Share This Article:

Links between Insulin Resistance, Lipoprotein Metabolism and Amyloidosis in Alzheimer’s Disease

Abstract Full-Text HTML XML Download Download as PDF (Size:1921KB) PP. 1549-1579
DOI: 10.4236/health.2014.612190    4,458 Downloads   5,809 Views   Citations


The origins of premature brain aging and chronic disease progression are associated with atherogenic diets and sedentary lifestyles in Western communities. Interests in brain aging that involves non alcoholic fatty liver disease (NAFLD), the global stroke epidemic and neurodegeneration have become the focus of nutritional research. Atherogenic diets have been linked to plasma ceramide dysregulation and insulin resistance actively promoting chronic diseases and neurodegeneration in developed countries. Abnormal lipid signaling as observed in chronic diseases such as hypothyroidism, obesity and diabetes is connected to stroke and neurodegenerative diseases in man. Lipids that are involved in calcium and amyloid betahomeostasis are critical to cell membrane stability with the maintenance of nuclear receptors and transcriptional regulators that are involved in cell chromatin structure and DNA expression. Western diets high in fat induce hyperlipidemia, insulin resistance and other hormonal imbalances that are linked to alterations in brain calcium and lipid metabolism with susceptibility to various chronic diseases such as stroke. Nutrition and food science research identifies dietary components and lipids to prevent hyperlipidemia and calcium dyshomeostasis connected to neuroendocrine disease by maintaining astrocyte-neuron interactions and reversing hormonal imbalances that are closely associated with NAFLD, stroke and Alzheimer’s disease (AD) in global populations.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Martins, I. and Creegan, R. (2014) Links between Insulin Resistance, Lipoprotein Metabolism and Amyloidosis in Alzheimer’s Disease. Health, 6, 1549-1579. doi: 10.4236/health.2014.612190.


[1] Blennow, K., de Leon, M.J. and Zetterberg, H. (2006) Alzheimer’s Disease. The Lancet, 368, 387-403. 69113-7
[2] Roses, A., Alberts, M. and Strittmatter, W. (1992) Alzheimer’s Disease—Reassessing the Data. Current Biology, 2, 7-9. 90400-5
[3] Brookmeyer, R., Johnson, E., Ziegler-Graham, K. and Arrighi, H.M. (2007) Forecasting the Global Burden of Alzheimer’s Disease. Alzheimer’s Dementia: The Journal of the Alzheimer’s Association, 3, 186-191.
[4] Ferri, C.P., Prince, M., Brayne, C., Brodaty, H., Fratiglioni, L., Ganguli, M., et al. (2005) Global Prevalence of Dementia: A Delphi Consensus Study. The Lancet, 366, 2112-2117. 67889-0
[5] Access, Delaying Onset of Alzheimer’s Disease: Predictions and Issues (Internet). 2004-2009 Report No. 30.
[6] Luchsinger, J.A. and Mayeux, R. (2004) Dietary Factors and Alzheimer’s Disease. The Lancet Neurology, 3, 579-587. 00878-6
[7] Scarmeas, N., Stern, Y., Tang, M.X., Mayeux, R. and Luchsinger, J.A. (2006) Mediterranean Diet and Risk for Alzheimer’s Disease. Annals of Neurology, 59, 912-921.
[8] Gu, Y., Nieves, J.W., Stern, Y., Luchsinger, J.A. and Scarmeas, N. (2010) Food Combination and Alzheimer Disease Risk: A Protective Diet. Archives of Neurology, 67, 699-706.
[9] Dietschy, J.M. (1998) Dietary Fatty Acids and the Regulation of Plasma Low Density Lipoprotein Cholesterol Concentrations. Journal of Nutrition, 128, 444S-448S.
[10] Woollett, L.A., Spady, D.K. and Dietschy, J.M. (1992) Regulatory Effects of the Saturated Fatty Acids 6:0 through 18:0 on Hepatic Low Density Lipoprotein Receptor Activity in the Hamster.TheJournal of Clinical Investigation, 89, 1133-1141.
[11] Woollett, L.A., Spady, D.K. and Dietschy, J.M. (1992) Saturated and Unsaturated Fatty Acids Independently Regulate Low Density Lipoprotein Receptor Activity and Production Rate. Journal of Lipid Research, 33, 77-88.
[12] Prudovsky, I., Vary, C.P.H., Markaki, Y., Olins, A.L. and Olins, D.E. (2012) Phosphatidylserine Colocalizes with Epichromatin in Interphase Nuclei and Mitotic Chromosomes. Nucleus, 3, 200-210.
[13] Tata, J.R., Hamilton, M.J. and Cole, D.R. (1972) Membrane Phospholipids Associated with Nuclei and Chromatin: Melting Profile, Template Activity and Stability of Chromatin. Journal of Molecular Biology, 67, 231-236. 90238-0
[14] Viiri, K., Mäki, M. and Lohi, O. (2012) Phosphoinositides as Regulators of Protein-Chromatin Interactions. Science Signaling, 5, pe19.
[15] Jones, D.R. and Divecha, N. (2004) Linking Lipids to Chromatin. Current Opinion Genetic Development, 14, 196-202.
[16] Laclette, J.P. and Montal, M. (1977) Interaction of Calcium with Negative Lipids in Planar Bilayer Membranes. Influence of the Solvent. Biophysical Journal, 19, 199-202. 85581-1
[17] Verdaguer, N., Corbalan-Garcia, S., Ochoa, W.F., Fita, I. and Gómez-Fernánde, J.C. (1999) Ca2+ Bridges the C2 Membrane-Binding Domain of Protein Kinase Cα Directly to Phosphatidylserine. The EMBO Journal, 18, 6329-6338.
[18] Bazan, N.G. (2005) Lipid Sigaling in Neural Plasticity, Brain Repair, and Neuroprotection. Molecular Neurobiology, 32, 89-103.
[19] Wymann, M.P. and Schneiter, R. (2008) Lipid Signalling in Disease. Nature Review Molecular Cellular Biology, 9, 162-176.
[20] Fernandis, A.Z. and Wenk, M.R. (2007) Membrane Lipids as Signaling Molecules. Current Opinion Lipidology, 18, 121-128.
[21] Verdile, G., Fuller, S., Atwood, C.S., Laws, S.M., Gandy, S.E. and Martins, R.N. (2004) The Role of Beta Amyloid in Alzheimer’s Disease: Still a Cause of Everything or the Only One Who Got Caught? Pharmacology Research, 50, 397-409.
[22] Attems, J., Quass, M., Jellinger, K.A. and Lintner, F. (2007) Topographical Distribution of Cerebral Amyloid Angiopathy and Its Effect on Cognitive Decline Are Influenced by Alzheimer Disease Pathology. Journal of the Neurological Science, 257, 49-55.
[23] Di Paolo, G. and Kim, T.W. (2011) Linking Lipids to Alzheimer’s Disease: Cholesterol and Beyond. Nature Reveiw Neuroscience, 12, 284-296.
[24] Martins, I.J., Berger, T., Sharman, M.J., Verdile, G., Fuller, S.J. and Martins. R/N. (2009) Cholesterol Metabolism and Transport in the Pathogenesis of Alzheimer’s Disease. Journal of Neurochemistry, 111, 1275-1308.
[25] Martins, I.J., Hone, E., Foster, J.K., Sünram-Lea, S.I., Gnjec, A., Fuller, S.J., et al. (2006) Apolipoprotein E, Cholesterol Metabolism, Diabetes and the Convergence of Risk Factors for Alzheimer’s Disease and Cardiovascular Disease. Molecular Psychiatry, 11, 721-736.
[26] Piomelli, D., Astarita, G. and Rapaka, R. (2007) A Neuroscientist’s Guide to Lipidomics. Nature Reveiw Neuroscience, 8, 743-754.
[27] Roher, A.E., Kuo, Y.M., Kokjohn, K.M., Emmerling, M.R. and Gracon, S. (1999) Amyloid and Lipids in the Pathology of Alzheimer’s Disease. Amyloid, 6, 136-145.
[28] Kuo, Y.M., Emmerlingb, M.R., Bisgaierc, C.L., Essenburgc, A.D., Lamperta, H.C., Drumm, D., et al. (1998) Elevated Low Density Lipoprotein in Alzheimer’s Disease Correlates with Brain Abeta 1-42 Levels. Biochimica Biophysica Research Communications, 252, 711-715.
[29] Merched, A., Xia, Y., Visvikis, S., Serot, J.M. and Siest, G. (2000) Decreased High-Density Lipoprotein Cholesterol and Serum Apolipoprotein AI Concentrations Are Highly Correlated with the Severity of Alzheimer’s Disease. Neurobiology Ageing, 21, 27-30. 00103-7
[30] Selkoe, D.J. (2004) Cell Biology of Protein Misfolding: The Examples of Alzheimer’s and Parkinson’s Diseases. Nature Cell Biology, 6, 1054-1061.
[31] Wenk, M.R. (2005) The Emerging Field of Lipidomics. Nature Reveiw Drug Discovery, 4, 594-610.
[32] Craft, S. (2009) The Role of Metabolic Disorders in Alzheimer Disease and Vascular Dementia: Two Roads Converged. Archives of Neurology, 66, 300-305.
[33] Farooqui, A.A., Farooqui, T., Panza, F. and Frisardi, V. (2012) Metabolic Syndrome as a Risk Factor for Neurological Disorders. Cell and Molecular Life Science, 69, 741-762.
[34] Frisardi, V. and Imbimbo B.P. (2012) Metabolic-Cognitive Syndrome: Metabolic Approach for the Management of Alzheimer’s Disease Risk. Journal of Alzheimer’s Disease, 30, S1-S4.
[35] Merlo, S., Spampinato, S., Canonico, P.L., Copani, A. and Sortino, M.A. (2010) Alzheimer’s Disease: Brain Expression of a Metabolic Disorder? Trends in Endocrinology & Metabolism, 21, 537-544.
[36] Luchsinger, J.A. (2012) Type 2 Diabetes and Cognitive Impairment: Linking Mechanisms. Journal of Alzheimer’s Disease, 30, S185-S198.
[37] Moreira, P.I. (2012) Alzheimer’s Disease and Diabetes: An Integrative View of the Role of Mitochondria, Oxidative stress, and Insulin. Journal of Alzheimer’s Disease, 30, S199-S215.
[38] Craft, S. (2005) Insulin Resistance Syndrome and Alzheimer’s Disease: Age- and Obesity-Related Effects on Memory, Amyloid, and Inflammation. Neurobiology of Ageing, 26, 65-69.
[39] Watson, G.S. and Craft, S. (2003) The Role of Insulin Resistance in the Pathogenesis of Alzheimer’s Disease: Implications for Treatment. Central Nervous System Drugs, 17, 27-45.
[40] De Felice, F.G., Lourenco, M.V. and Ferreira, S.T. (2014) How Does Brain Insulin Resistance Develops in Alzheimer’s Disease? Alzheimers Dementia, 10, S26-S32.
[41] Chiu, S.L., Chen, C.M. and Cline, H.T. (2008) Insulin Receptor Signaling Regulates Synapse Number, Dendritic Plasticity, and Circuit Function in Vivo. Neuron, 58, 708-719.
[42] Shoelson, S.E., Lee, J. and Goldfine, A.B. (2006) Inflammation and Insulin Resistance. Journal Clinical Investigation, 116, 1793-1801.
[43] Rizos, C.V., Elisaf, M.S. and Liberopoulos, E.N. (2001) Effects of Thyroid Dysfunction on Lipid Profile. The Open Cardiovascular Medical Journal, 5, 76-84.
[44] Quinlan, P., Nordlund, A., Lind, K., Gustafson, D., Edman, Å. and Wallin A. (2010) Thyroid Hormones Are Associated with Poorer Cognition in Mild Cognitive Impairment. Dementia Geriatric Cognition Disorder, 30, 205-211.
[45] Martins, I.J., Creegan, R., Lim, W.L.F. and Martins, R.N. (2013) Molecular Insights into Appetite Control and Neuroendocrine Disease as Risk Factors for Chronic Diseases in Western Countries. Open Journal of Endocrine and Metabolic Diseases, 3, 11-33.
[46] Burgess, B.L., McIsaac, S.A, Naus, K.E., Chan, J.Y., Tangsley, G.H., Yang, J., et al. (2006) Elevated plasma triglyceride levels precede amyloid deposition in Alzheimer's disease mouse models with abundant A beta in plasma. Neurobiology of Disease, 24, 114-127.
[47] Chavez, J.A. and Summers, S.A. (2012) A Ceramide-Centric View of Insulin Resistance. Cell Metabolism, 15, 585-594.
[48] Summers, S.A. (2006) Ceramides in Insulin Resistance and Lipotoxicity. Progress in Lipid Research, 45, 42-72.
[49] Kowalski, G.M., Carey, A.L., Selathurai, A., Kingwell, B.A. and Bruce, C.R. (2013) Plasma Sphingosine-1-Phosphate Is Elevated in Obesity. PLoS ONE, 8, e72449.
[50] Hammad, S.M., Al Gadban, M.M., Semler, A.J. and Klein, R.L. (2012) Sphingosine 1-Phosphate Distribution in Human Plasma: Associations with Lipid Profiles. Journal of Lipids, 2012, Article ID: 180705.
[51] Samad, F., Hester, K.D., Yang, G., Hannun, Y.A. and Bielawski, J. (2006) Altered Adipose and Plasma Sphingolipid Metabolism in Obesity: A Potential Mechanism for Cardiovascular and Metabolic Risk. Diabetes, 55, 2579-2587.
[52] Blachnio-Zabielska, A.U., Koutsari, C., Tchkonia, T. and Jensen, M.D. (2012) Sphingolipid Content of Human Adipose Tissue: Relationship to Adiponectin and Insulin Resistance. Obesity (Silver Spring) , 20, 2341-2347.
[53] Bikman, B.T. (2012) A Role for Sphingolipids in the Pathophysiology of Obesity-Induced Inflammation. Cellular and Molecular Life Sciences, 69, 2135-2146.
[54] Kang, S.C., Kim, B.R., Lee, S.Y. and Park, T.S. (2013) Sphingolipid Metabolism and Obesity-Induced Inflammation. Frontiers in Endocrinology (Lausanne) , 4, 67.
[55] Wilkerson, B.A., Grass, G.D., Wing, S.B., Argraves, W.S. and Argraves, K.M. (2012) Sphingosine 1-Phosphate (S1P) Carrier-Dependent Regulation of Endothelial Barrier: High Density Lipoprotein (HDL) -S1P Prolongs Endothelial Barrier Enhancement as Compared with Albumin-S1P via Effects on Levels, Trafficking, and Signaling of S1P1. TheJournal of Biological Chemistry, 287, 44645-44653.
[56] Murata, N., Sato, K., Kon, J., Tomura, H., Yanagita, M., Kuwabara, A., et al. (2000) Interaction of Sphingosine 1-Phosphate with Plasma Components, Including Lipoproteins, Regulates the Lipid Receptor-Mediated Actions. Biochemical Journal, 352, 809-815.
[57] Sattler, K. and Levkau, B. (2009) Sphingosine-1-Phosphate as a Mediator of High-Density Lipoprotein Effects in Cardiovascular Protection. Cardiovascular Research, 82, 201-211.
[58] Dahm, F., Nocito, A., Bielawska, A., Lang, K.S., Georgiev, P., Asmis, L.M., et al. (2006) Distribution and Dynamic Changes of Sphingolipids in Blood in Response to Platelet Activation. Journal of Thrombosis and Haemostasis, 4, 2704-2709.
[59] Tao, R.V., Sweeley, C.C. and Jamieson, G.A. (1973) Sphingolipid Composition of Human Platelets. Journal of Lipid Research, 14, 16-25.
[60] Saniabadi, A.R., Umemura, K., Shimoyama, M., Adachi, M., Nakano, M. and Nakashima, M. (1997) Aggregation of Human Blood Platelets by Remnant Like Lipoprotein Particles of Plasma Chylomicrons and Very Low Density Lipoproteins. Thrombosis Haemostasis, 77, 996-1001.
[61] Relou, I.A., Hackeng, C.M., Akkerman, J.W. and Malle, E. (2003) Low-Density Lipoprotein and Its Effect on Human Blood Platelets. Cell Molecular& Life Science, 60, 961-971.
[62] Anfossi, G., Russo, I. and Trovati, M. (2009) Platelet Dysfunction in Central Obesity. Nutrition, Metabolism & Cardiovascular Disease, 19, 440-449.
[63] Santilli, F., Vazzana, N., Liani, R., Guagnano, M.T. and Davì, G. (2011) Platelet Activation in Obesity and Metabolic Syndrome. Obesity Reviews, 13, 27-42.
[64] Casoli, T., Di Stefano, G., Giorgetti, B., Grossi, Y., Balietti, M., Fattoretti, P. and Bertoni-Freddari, C. (2007) Release of Beta-Amyloid from High-Density Platelets: Implications for Alzheimer’s Disease Pathology. Annuals of the New York Academy of Science, 1096, 170-178.
[65] Chen, M., Inestrosa, N.C., Ross, G.S. and Fernandez, H.L. (1995) Platelets Are the Primary Source of Amyloid Beta-Peptide in Human Blood. Biochemical & Biophysic Research Communications, 213, 96-103.
[66] Park, T.S., Hu, Y., Noh, H.L., Drosatos, K., Okajima, K., Buchanan, J., et al. (2008) Ceramide Is a Cardiotoxin in Lipotoxic Cardiomyopathy. Journal of Lipid Research, 49, 2101-2112.
[67] Bikman, B.T. and Summers, S.A. (2011) Ceramides as Modulators of Cellular and Whole-Body Metabolism. Journal of Clinical Investigation, 121, 4222-4230.
[68] Ussher, J.R., Koves, T.R., Cadete, V.J., Zhang, L., Jaswal, J.S., Swyrd, S.J., et al. (2010) Inhibition of De Novo Ceramide Synthesis Reverses Diet-Induced Insulin Resistance and Enhances Whole-Body Oxygen Consumption. Diabetes, 59, 2453-2464.
[69] Galadari, S., Rahman, A., Pallichankandy, S., Galadari, A. and Thayyullathil, F. (2013) Role of Ceramide in Diabetes Mellitus: Evidence and Mechanisms. Lipids in Health Disease, 12, 98.
[70] Schmitz-Peiffer, C. (2010) Targeting Ceramide Synthesis to Reverse Insulin Resistance. Diabetes, 59, 2351-2353.
[71] Costantini, C., Kolasani, R.M. and Puglielli, L. (2005) Ceramide and Cholesterol: Possible Connections between Normal Ageing of the Brain and Alzheimer’s Disease. Just Hypotheses or Molecular Pathways to Be Identified? Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, 1, 43-50.
[72] Hussain, M.M., Jin, W. and Jiang, X.C. (2012) Mechanisms Involved in Cellular Ceramide Homeostasis. Nutrition & Metabolism (London) , 9, 71.
[73] Filippov, V., Song, M.A., Zhang, K., Vinters, H.V., Tung, S., Kirsch, W.M., et al. (2012) Increased Ceramide in Brains with Alzheimer’s and Other Neurodegenerative Diseases. Journal of Alzheimer’s Disease, 29, 537-547.
[74] Satoi, H., Tomimoto, H., Ohtani, R., Kitano, T., Kondo, T., Watanabe, M., et al. (2005) Astroglial Expression of Ceramide in Alzheimer’s Disease Brains: A Role during Neuronal Apoptosis. Neuroscience, 130, 657-666.
[75] Mielke, M.M., Bandaru, V.V., Haughey, N.J., Xia, J., Fried, L.P., Yasar, S., et al. (2012) Serum Ceramides Increase the Risk of Alzheimer Disease: The Women’s Health and Ageing Study II. Neurology, 14, 633-641.
[76] Yuyama, K., Mitsutake, S. and Igarashi, Y. (2013) Pathological Roles of Ceramide and Its Metabolites in Metabolic Syndrome and Alzheimer’s Disease.Biochimica et Biophysica Acta (BBA) , Molecular and Cell Biology of Lipids, 1841, 793-798.
[77] Corder, E.H., Saunders, A.M., Strittmatter, W.J., Schmechel, D.E., Gaskell, P.C., Small, G.W., et al. (1993) Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer’s Disease in Late onset Families. Science, 261, 921-923.
[78] Saunders, A.M., Strittmatter, W.J., Schmechel, D., St. George-Hyslop, P.H., Pericak-Vance, M.A., Joo, S.H., et al. (1993) Association of Apolipoprotein E Allele Epsilon 4 with Late-Onset Familial and Sporadic Alzheimer’s Disease. Neurology, 43, 1467-1472.
[79] Rall, S.C., Weisgraber, K.H. and Mahley, R.W. (1982) Human Apolipoprotein E. The Complete Amino Acid Sequence. Journal of Biological Chemistry, 257, 4171-4178.
[80] Weisgraber, K.H., Innerarity, T.L. and Mahley, R.W. (1982) Abnormal Lipoprotein Receptor-Binding Activity of the Human E Apoprotein Due to Cysteine-Arginine Interchange at a Single Site. Journal of Biological Chemistry, 257, 2518-2521.
[81] Mahley, R.W. and Huang, Y. (1999) Apolipoprotein E: From Atherosclerosis to Alzheimer’s Disease and Beyond. Current Opinion in Lipidology, 10, 207-217.
[82] Feussner, G., Feussner, V., Hoffmann, M.M., Lohrmann, J., Wieland, H. and M?rz, W. (1998) Molecular Basis of Type III Hyperlipoproteinemia in Germany. Human Mutation, 11, 417-423.
[83] Huang, X., Chen, P.C. and Poole, C. (2004) APOE-[Epsilon]2 Allele Associated with Higher Prevalence of Sporadic Parkinson Disease. Neurology, 62, 2198-2202.
[84] Strittmatter, W.J., Saunders, A.M., Schmechel, D., Pericak-Vance, M., Enghild, J., Salvesen, G.S., et al. (1993) Apolipoprotein E: High-Avidity Binding to Beta-Amyloid and Increased Frequency of Type 4 Allele in Late-Onset Familial Alzheimer Disease. Proceedings of the National Academy of Sciences of the United States of America, 90, 1977-1981.
[85] Deary, I.J., Whiteman, M.C., Pattie, A., Starr, J.M., Hayward, C., Wright, A.F., et al. (2002) Cognitive Change and the APOE Epsilon 4 Allele. Nature, 418, 932.
[86] Chapman, J., Vinokurov, S., Achiron, A., Karussis, D.M., Mitosek-Szewczyk, K., Birnbaum, M., et al. (2011) APOE Genotype Is a Major Predictor of Long-Term Progression of Disability in MS. Neurology, 56, 312-316.
[87] McCarron, M.O., Delong, D. and Alberts, M.J. (1999) APOE Genotype as a Risk Factor for Ischemic Cerebrovascular Disease: A Meta-Analysis. Neurology, 53, 1308-1311.
[88] Kadotani, H., Kadotani, T., Young, T., Peppard, P.E., Finn, L., Colrain, I.M., et al. (2001) Association between Apolipoprotein E Epsilon4 and Sleep-Disordered Breathing in Adults. Journal of American Medical Association, 285, 2888-2890.
[89] Gottlieb, D.J., DeStefano, A.L., Foley, D.J., Mignot, E., Redline, S., Givelber, R.J., et al. (2004) APOE Epsilon4 Is Associated with Obstructive Sleep Apnea/Hypopnea: The Sleep Heart Health Study. Neurology, 63, 664-668.
[90] Martins, R.N., Clarnette, R., Fisher, C., Broe, G.A., Brooks, W.S., Montgomery, P., et al. (1995) ApoE Genotypes in Australia: Roles in Early and Late Onset Alzheimer’s Disease and Down’s Syndrome. Neuroreport, 6, 1513-1516.
[91] Bales, K.R., Dodart, J.C., DeMattos, R.B., Holtzman, D.M. and Paul, S.M. (2002) Apolipoprotein E, Amyloid, and Alzheimer Disease. Molecular Interventions, 2, 363-375.
[92] Zheng, H. and Koo, E.H. (2006) The Amyloid Precursor Protein: Beyond Amyloid. Molecular Neurodegeneration, 1, 5.
[93] Beel, A.J., Sakakura, M., Barrett, P.J. and Sanders, C.R. (2010) Direct Binding of Cholesterol to the Amyloid Precursor Protein: An Important Interaction in Lipid-Alzheimer’s Disease Relationships? Biochimica et Biophysica Acta (BBA) , Molecular and Cell Biology of Lipids, 1801, 975-982.
[94] Korade, Z. and Kenworthy, A.K. (2008) Lipid Rafts, Cholesterol, and the Brain. Neuropharmacology, 55, 1265-1273.
[95] Zhang, Y.W. and Xu, H. (2007) Molecular and Cellular Mechanisms for Alzheimer’s Disease: Understanding APP Metabolism. Current Molecular Medicine, 7, 687-696.
[96] O’Brien, R.J. and Wong P.C. (2011) Amyloid Precursor Protein Processing and Alzheimer’s Disease. Annual Reveiw Neuroscience, 34, 185-204.
[97] Zhang, Y.W., Thompson, R., Zhang, H. and Xu, H. (2011) APP Processing in Alzheimer’s Disease. Molecular Brain, 4, 1-13.
[98] Zhang, Q., Yang, G., Li, W., Fan, Z., Sun, A., Luo, J. and Ke, Z.J. (2011) Thiamine Deficiency Increases Beta-Secretase Activity and Accumulation of Beta-Amyloid Peptides. Neurobiology of Ageing, 32, 42-53.
[99] Puglielli, L., Ellis, B.C., Saunders, A.J. and Kovacs, D.M. (2002) Ceramide Stabilizes Beta-Site Amyloid Precursor Protein-Cleaving Enzyme 1 and Promotes Amyloid Beta-Peptide Biogenesis. Journal of Biological Chemistry, 278, 19777-19783.
[100] Li, H., Kim, W.S., Guillemin, G.J., Hill, A.F., Evin, G. and Garner, B. (2010) Modulation of Amyloid Precursor Protein Processing by Synthetic Ceramide Analogues. Biochimca et Biophysica Acta (BBA) , Molecular and Cell Biology of Lipids, 1801, 887-895
[101] Takasugi, N., Sasaki, T., Suzuki, K., Osawa, S., Isshiki, H., Hori, Y., et al. (2011) BACE1 Activity Is Modulated by Cell-Associated Sphingosine-1-Phosphate. The Journal of Neuroscience, 31, 6850-6857.
[102] Gassowska, M., Cieslik, M., Wilkaniec, A. and Strosznajder, J.B. (2014) Sphingosine Kinases/Sphingosine-1-Phosphate and Death Signalling in APP-Transfected Cells. Neurochemical Research, 39, 645-652.
[103] Maysinger, D., Holmes, M., Han, X., Epand, R.M., Pertens, E., Foerster, A., et al. (2008) Ceramide Is Responsible for the Failure of Compensatory Nerve Sprouting in Apolipoprotein E Knock-Out Mice. Journal of Neuroscience, 28, 7891-7899.
[104] Jeong, T.S., Schissel, S.L. Tabas, I., Pownall, H.J., Tall, A.R. and Jiang, X. (1998) Increased Sphingomyelin Content of Plasma Lipoproteins in Apolipoprotein E Knockout Mice Reflects Combined Production and Catabolic Defects and Enhances Reactivity with Mammalian Sphingomyelinase. Journal of Clinical Investigation, 101, 905-912.
[105] Bandaru, V.V., Troncoso, J., Wheeler, D., Pletnikova, O., Wang, J., Conant, K., et al. (2004) ApoE4 Disrupts Sterol and Sphingolipid Metabolism in Alzheimer’s but Not Normal Brain. Neurobiology of Ageing, 30, 591-599.
[106] Reitz, C., Tang, M.X., Luchsinger, J. and Mayeux, R.(2004) Relation of Plasma Lipids to Alzheimer Disease and Vascular Dementia. Archives of Neurology, 61, 705-714.
[107] Hayden, K.M., Zandi, P.P., Lyketsos, C.G., Khachaturian, A.S., Bastian, L.A., Charoonruk, G., et al. (2006) Vascular Risk Factors for Incident Alzheimer Disease and Vascular Dementia: The Cache County Study. Alzheimer Disease & Association Disorders, 20, 93-100.
[108] Reitz, C., Tang, M.X., Schupf, N., Manly, J.J., Mayeux, R. and Luchsinger, J.A. (2010) Association of Higher Levels of High-Density Lipoprotein Cholesterol in Elderly Individuals and Lower Risk of Late-Onset Alzheimer Disease. Archives of Neurology, 67, 1491-1497.
[109] Bowman, G.L., Kaye, J.A. and Quinn, J.F. (2012) Dyslipidemia and Blood-Brain Barrier Integrity in Alzheimer’s Disease. Current Gerontology and Geriatric Research, 2012, 1-5.
[110] Jiang, X.C., Bruce, C., Mar, J., Lin, M., Ji, Y., Francone, O.L., et al. (1999) Targeted Mutation of Plasma Phospholipid Transfer Protein Gene Markedly Reduces High-Density Lipoprotein Levels. Journal Clinical Investigation, 103, 907-914.
[111] Qin, S., Kawano, K., Bruce, C., Lin, M., Bisgaier, C., Tall, A.R., et al. (2000) Phospholipid Transfer Protein Gene Knock-Out Mice Have Low High Density Lipoprotein Levels, Due to Hypercatabolism, and Accumulate apoA-IV-Rich Lamellar Lipoproteins. Journal of Lipid Research, 41, 269-276.
[112] Jiang, X.C., Jin, W. and Hussain, M.M. (2012) The Impact of Phospholipid Transfer Protein (PLTP) on Lipoprotein Metabolism. Nutrition& Metabolism (London) , 9, 75.
[113] Levels, J.H., Marquart, J.A., Abraham, P.R., van den Ende, A.E., Molhuizen, H.O., van Deventer, S.J., et al. (2005) Lipopolysaccharide Is Transferred from High-Density to Low-Density Lipoproteins by Lipopolysaccharide-Binding Protein and Phospholipid Transfer Protein. Infection and Immunity, 73, 2321-2326.
[114] Rao, R., Albers, J.J., Wolfbauer, G. and Pownall, H.J. (1997) Molecular and Macromolecular Specificity of Human Plasma Phospholipid Transfer Protein. Biochemistry, 36, 3645-3653.
[115] Wang, H., Yu, Y., Chen, W., Cui, Y., Luo, T., Ma, J., et al. (2014) PLTP Deficiency Impairs Learning and Memory Capabilities Partially Due to Alteration of Amyloid-β Metabolism in Old Mice. Journal of Alzheimer’s Disease, 39, 79-88
[116] Desrumaux, C., Pisoni, A., Meunier, J., Deckert, V., Athias, A., Perrier, V., et al. (2013) Increased Amyloid-β Peptide-Induced Memory Deficits in Phospholipid Transfer Protein (PLTP) Gene Knockout Mice. Neuropsychopharmacology, 38, 817-825.
[117] Desrumaux, C., Risold, P.Y., Schroeder, H., Deckert, V., Masson, D., Athias, A., et al. (2005) Phospholipid Transfer Protein (PLTP) Deficiency Reduces Brain Vitamin E Content and Increases Anxiety in Mice. FASEB Journal, 19, 296-297.
[118] Yang, C.Y., Raya, J.L., Chen, H.H., Chen, C.H., Abe, Y., Pownall, H.J., et al. (2003) Isolation, Characterization, and Functional Assessment of Oxidatively Modified Subfractions of Circulating Low-Density Lipoproteins. Arteriosclerosis, Thrombosis, and Vascular Biology, 23, 1083-1090.
[119] Huuskonen, J. and Ehnholm, C. (2000) Phospholipid Transfer Protein in Lipid Metabolism. Current Opinion in Lipidology, 11, 285-289.
[120] Huuskonen, J., Olkkonen, V.M., Ehnholm, C., Metso, J., Julkunen, I. and Jauhiainen, M. (2000) Phospholipid Transfer Is a Prerequisite for PLTP-Mediated HDL Conversion. Biochemistry, 39, 16092-16098.
[121] Demeester, N., Castro, G., Desrumaux, C., De Geitere, C., Fruchart, J.C., Santens, P., et al. (2000) Characterization and Functional Studies of Lipoproteins, Lipid Transfer Proteins, and Lecithin: Cholesterol Acyltransferase in CSF of Normal Individuals and Patients with Alzheimer’s Disease. Journal Lipid Research, 41, 963-974.
[122] Dullaart, R.P., van Tol, A. and Dallinga-Thie, G.M. (2013) Phospholipid Transfer Protein, an Emerging Cardiometabolic Risk Marker: Is It Time to Intervene? Atherosclerosis, 228, 38-41.
[123] Robins, S.J., Lyass, A., Brocia, R.W., Massaro, J.M. and Vasan, R.S. (2013) Plasma Lipid Transfer Proteins and Cardiovascular Disease. The Framingham Heart Study. Atherosclerosis, 228, 230-236.
[124] Schlitt, A., Bickel, C., Thumma, P., Blankenberg, S., Rupprecht, H.J., Meyer, J., et al. (2003) High Plasma Phospholipid Transfer Protein Levels as a Risk Factor for Coronary Artery Disease. Arteriosclerosis Thrombosis, Thrombosis, and Vascular Biology, 23, 1857-1862.
[125] Yatsuya, H., Tamakoshi, K., Hattori, H., Otsuka, R., Wada, K., Zhang, H., et al. (2004) Serum Phospholipid Transfer Protein Mass as a Possible Protective Factor for Coronary Heart Diseases. Circulation Journal, 68, 11-16.
[126] Schgoer, W., Mueller, T., Jauhiainen, M., Wehinger, A., Gander, R., Tancevski, I., et al. (2008) Low Phospholipid Transfer Protein (PLTP) Is a Risk Factor for Peripheral Atherosclerosis. Atherosclerosis, 196, 219-226.
[127] van Tol, A. (2002) Phospholipid Transfer Protein. Current Opinion in Lipidology, 13, 135-139.
[128] Tall, A.R., Abreu, E. and Shuman, J. (1983) Separation of a Plasma Phospholipid Transfer Protein from Cholesterol Ester/Phospholipid Exchange Protein. Journal of Biological Chemistry, 258, 2174-2180.
[129] Lightle, S., Tosheva, R., Leea, A., Queen-Bakera, J., Boyanovsky, B., Shedlofsky, S., et al. (2003) Elevation of Ceramide in Serum Lipoproteins during Acute Phase Response in Humans and Mice: Role of Serine-Palmitoyl Transferase. Archives of Biochemistry and Biophysics, 419, 120-128.
[130] Nikolova-Karakashian, M.N. (2002) CHAPTER 15, Ceramide in Serum Lipoproteins: Function and Regulation of Metabolism. In: Futerman, A.H., Ed., Ceramide Signaling, and Kluwer Academic/Plenum Publishers, New York.
[131] Hanada, K., Kumagai, K., Tomishige, N. and Kawano, M. (2007) CERT and Intracellular Trafficking of Ceramide. Biochimica et Biophysica Acta (BBA) , Molecular and Cell Biology of Lipids, 1771, 644-653.
[132] Pinto, S.N., Silva, L.C., Futerman, A.H. and Prieto, M. (2011) Effect of Ceramide Structure on Membrane Biophysical Properties: The Role of Acyl Chain Length and Unsaturation. Biochimica et Biophysica Acta (BBA) , Biomembranes, 1808, 2753-2760.
[133] Huuskonen, J., Olkkonen, V.M., Jauhiainen, M., Metso, J., Somerharju, P. and Ehnholm, C. (1996) Acyl Chain and Headgroup Specificity of Human Plasma Phospholipid Transfer Protein. Biochimica et Biophysica Acta (BBA) , Lipids and Lipid Metabolism, 1303, 207-214. 00103-8
[134] Kontush, A., Therond, P., Zerrad, A., Couturier, M., Négre-Salvayre, A., de Souza, J.A., et al. (2007) Preferential Sphingosine-1-Phosphate Enrichment and Sphingomyelin Depletion Are Key Features of Small Dense HDL3 Particles: Relevance to Antiapoptotic and Antioxidative Activities. Arteriosclerosis Thrombosis, Thrombosis, and Vascular Biology, 27, 1843-1849.
[135] Takabe, K., Paugh, S.W., Milstien, S. and Spiegel, S. (2008) “Inside-Out” Signaling of Sphingosine-1-Phosphate: Therapeutic Targets. Pharmacological Review, 60, 181-195.
[136] Yu, Y., Guo, S., Feng, Y., Feng, L., Cui, Y., Song, G., et al. (2014) Phospholipid Transfer Protein Deficiency Decreases the Content of S1P in HDL via the Loss of Its Transfer Capability. Lipids, 49, 183-190.
[137] Pfreiger, F.W. and Ungerer, N. (2011) Cholesterol Metabolism in Neurons and Astrocytes. Progress in Lipid Research, 50, 357-371.
[138] Pfrieger, F.W. (2003) Outsourcing in the Brain: Do Neurons Depend on Cholesterol Delivery by Astrocytes? BioEssays, 25, 72-78.
[139] Smith, I.F., Green, K.N. and LaFerla, F.M. (2005) Calcium Dysregulation in Alzheimer’s Disease: Recent Advancesgained from Genetically Modified Animals. Cell Calcium, 38, 427-437.
[140] Hansson, E. and Rönnbäck, L.L. (2003) Glial Neuronal Signaling in the Central Nervous System. The FASEB Journal, 17, 341-348.
[141] Dringen, R., Gutterer, J.M. and Hirrlinger, J. (2000) Glutathione Metabolism in Brain. Metabolic Interaction between Astrocytes and Neurons in the Defense against Reactive Oxygen Species. European Journal of Biochemistry, 267, 4912-4916.
[142] Chen, Y., Vartiainen, N.E., Ying, W., Chan, P.H., Koistinaho, J. and Swanson, R.A. (2001) Astrocytes Protect Neurons from Nitric Oxide Toxicity by a Glutathione-Dependent Mechanism. Journal of Neurochemistry, 77, 1601-1610.
[143] Thal, D.R. (2012) The Role of Astrocytes in Amyloid β-Protein Toxicity and Clearance. Experimental Neurology, 236, 1-5.
[144] Meyer, R.P., Knotha, R., Schiltzb, E. and Volk, B. (2001) Possible Function of Astrocyte Cytochrome P450 in Control of Xenobiotic Phenytoin in the Brain: In Vitro Studies on Murine Astrocyte Primary Cultures. Experimental Neurology, 167, 376-384.
[145] Volk, B., Meyer, R.P. and Knoth, R. (2004) Chapter 4. Function of Astrocyte Cytochrome P450 in Control of Xenobiotic Metabolism. In: Aschner, M. and Lucio, G.C., Eds., The Role of Glia in Neurotoxicity, 2nd Edition, CRC Press, Boca Raton, 61-72.
[146] Harris, F.M., Tesseur, I., Brecht, W.J., Xu, Q., Mullendorff, K., Chang, S., et al. (2004) Astroglial Regulation of Apolipoprotein E Expression inNeuronal Cells. The Journal of Biological Chemistry, 279, 3862-3868.
[147] Gee, J.R. and Keller, J.N. (2005) Astrocytes: Regulation of Brain Homeostasis via Apolipoprotein E. The International Journal Biochemistry & Cell Biology, 37, 1145-1150.
[148] Wang, X., Ciraolob, G., Morrisb, R. and Gruenstein, E. (1997) Identification of a Neuronal Endocytic Pathway Activated by an Apolipoprotein E (apoE) Receptor Binding Peptide. Brain Research, 778, 6-15. 00877-9
[149] Misra, U.K., Adlakha, C.L., Gawdi, G., McMillian, M.K., Pizzo, S.V. and Laskowitz, D.T. (2001) Apolipoprotein E and Mimetic Peptide Initiate a Calcium-Dependent Signaling Response in Macrophages. Journal of Leukocyte Biology, 70, 677-683.
[150] Morikawa, M., Fryera, J.D., Sullivanb, P.M., Christophera, E.A., Wahrlea, S.E., DeMattos, R.B., et al. (2005) Production and Characterization of Astrocyte-Derived Human Apolipoprotein E Isoforms from Immortalized Astrocytes and Their Interactions with Amyloid-Beta. Neurobiology of Disease, 19, 66-76.
[151] Sato, K., Malchinkhuu, E., Horiuchi, Y., Mogi, C., Tomura, H., Tosaka, M., et al. (2007) Critical Role of ABCA1 Transporter in Sphingosine 1-Phosphate Release from Astrocytes. Journal of Neurochemistry, 103, 2610-2619.
[152] Jänis, M.T., Metso, J., Lankinen, H., Strandin, T., Olkkonen, V.M., Rye, K.A., et al. (2005) Apolipoprotein E Activates the Low-Activity form of Human Phospholipid Transfer Protein. Biochemical and Biophysical Research Communications, 331, 333-340.
[153] Tan, K.C., Shiu, S.W.M., Wong, Y., Wong, W.K. and Tam, S. (2006) Plasma Apolipoprotein E Concentration Is an Important Determinant of Phospholipid Transfer Protein Activity in Type 2 Diabetes Mellitus. Diabetes/Metabolism Research and Review, 22, 307-312.
[154] Oram, J.F., Wolfbauer, G., Tang, C., Davidson, W.S. and Albers, J.J. (2008) An Amphipathic Helical Region of the N-Terminal Barrel of Phospholipid Transfer Protein Is Critical for ABCA1-Dependent Cholesterol Efflux. Journal of Biological Chemistry, 283, 11541-11549.
[155] Lalanne, F., Motta, C., Pafumi, Y., Lairon, D. and Ponsin, G. (2001) Modulation of the Phospholipid Transfer Protein-Mediated Transfer of Phospholipids by Diacylglycerols. The Journal of Lipid Research, 42, 142-149.
[156] Gabuzda, D., Busciglio, J. and Yankner, B.A. (1993) Inhibition of Beta-Amyloid Production by Activation of Protein Kinase C. Journal of Neurochemistry, 61, 2326-2329.
[157] Tanabe, F., Nakajima, T. and Ito, M. (2014) Involvement of Diacylglycerol Produced by Phospholipase D Activation in Aβ-Induced Reduction of sAPPα Secretion in SH-SY5Y Neuroblastoma Cells. Biochemistry and Biophysics Research Communication, 446, 933-939.
[158] Mungenast, A.E. (2011) Diacylglycerol Signaling Underlies Astrocytic ATP Release. Neural Plasticity, 2011, Article ID: 537659.
[159] Garwood, C.J., Pooler, A.M., Atherton, J., Hanger, D.P. and Noble, W. (2011) Astrocytes Are Important Mediators of Aβ-Inducedneurotoxicity and Tau Phosphorylation in Primary Culture. Cell Death and Disease, 2, e167.
[160] Nagele, R.G., D’Andrea, M.R., Lee, H., Venkataraman, V. and Wang, H.Y. (2003) Astrocytes Accumulate A Beta 42 and Give Rise to Astrocytic Amyloid Plaques in Alzheimer Disease Brains. Brain Research, 971, 197-209. 02361-8
[161] Wyss-Coray, T., Loike, J.D., Brionne, T.C., Lu, E., Anankov, R., Yan, F., et al. (2003) Adult Mouse Astrocytes Degrade Amyloid-β in Vitro and in Situ. Nature Medicine, 9, 453-457,
[162] Canepa, E., Borghi, R., Viña, J., Traverso, N., Gambini, J., Domenicotti, C., et al. (2011) Cholesterol and Amyloid-β: Evidence for a Cross-Talk between Astrocytes and Neuronal Cells. Journal of Alzheimer’s Disease, 25, 645-653.
[163] Ghering, A.B. and Davidson, W.S. (2006) Ceramide Structural Features Required to Stimulate ABCA1-Mediated Cholesterol Efflux to Apolipoprotein A-I. Journal of Lipid Research, 47, 2781-2788.
[164] Witting, S.R., Maiorano, N. and Davidson, W.S. (2003) Ceramide Enhances Cholesterol Efflux to Apolipoprotein A-I by Increasing the Cell Surface Presence of ATP-Binding Cassette Transporter A1.The Journal of Biological Chemistry, 278, 40121-40127.
[165] Martins, I.J., Lim, W.L.F., Wilson, A.C., Laws, S.M. and Martins, R.N. (2013) The Acceleration of Aging and Alzheimer’s Disease through the Biological Mechanisms Behind Obesity and Type II Diabetes. Health, 5, 913-992.
[166] Lim, F.L., Lam, S.M., Shui, G., Mondal, A., Ong, D., Duan, X., et al. (2013) Effects of a High-Fat, High-Cholesterol Diet on Brain Lipid Profiles in Apolipoprotein E ε3 and ε4 Knock-In Mice. Neurobiology of Aging, 34, 2217-2224.
[167] Frisardi, V., Panza, F., Seripa, D., Farooqui, T. and Farooqui, A.A. (2011) Glycerophospholipids and Glycerophospholipid-Derived Lipid Mediators: A Complex Meshwork in Alzheimer’s Disease Pathology. Progress in Lipid Research, 50, 313-330.
[168] Caggiula, A.W. and Mustad, V.A. (1997) Effects of Dietary Fat and Fatty Acids on Coronary Artery Disease Risk and total and Lipoprotein Cholesterol Concentrations: Epidemiologic Studies. American Journal of Clinical Nutrition, 65, 1597S-1610S.
[169] Kris-Etherton, P.M. and Yu, S. (1997) Individual Fatty Acid Effects on Plasma Lipids and Lipoproteins: Human Studies. American Journal Clinical Nutrition, 65, 1628S-1644S.
[170] Kris-Etherton, P.M., Yu, S., Etherton, T.D., Morgan, R., Moriarty, K. and Shaffer, D. (1997) Fatty Acids and Progression of Coronary Artery Disease. American Journal of Clinical Nutrition, 65, 1088-1090.
[171] Gill, J.M. and Sattar, N. (2009) Ceramides: A New Player in the Inflammation-Insulin Resistance Paradigm? Diabetologia, 52, 2475-2477.
[172] Espenshade, P.J. (2006) SREBPs: Sterol Regulated Transcription Factors. Journal of Cell Science, 119, 973-976.
[173] Spady, D.K., Woollett, L.A. and Dietschy, J.M. (1993) Regulation of Plasma LDL-Cholesterol Levels by Dietary Cholesterol and Fatty Acids. Annual Reveiw Nutrition, 13, 355-381.
[174] Worgall, T.S., Juliano, R.A., Seo, T. and Deckelbaum, R.J. (2004) Ceramide Synthesis Correlates with the Posttranscriptional Regulation of the Sterol-Regulatory Element-Binding Protein. Arteriosclerosis, Thrombosis, and Vascular Biology, 24, 943-948.
[175] Ascherio, A., Katan, M.B., Zock, P.L., Stampfer, M.J. and Willett, W.C. (1994) Trans Fatty Acids and Coronary Heart Disease. The New England Journal of Medicine, 340, 1994-1998.
[176] Morris, M.C., Evans, D.A., Bienias, J.L., Tangney, C.C., Bennett, D.A., Aggarwal, N., et al. (2003) Dietary Fats and the Risk of Incident Alzheimer Disease. Archives of Neurology, 60, 194-200.
[177] Bowman, G.L., Silbert, L.C., Howieson, D., Dodge, H.H., Traber, M.G., Frei, B., et al. (2012) Nutrient Biomarker Patterns, Cognitive Function, and MRI Measures of Brain Aging. Neurology, 78, 241-249.
[178] Mauger, J.F., Lichtenstein, A.H., Ausman, L.M., Jalbert, S.M., Jauhiainen, M., Ehnholm, C., et al. (2003) Effect of Different Forms of Dietary Hydrogenated Fats on LDL Particle Size. American Journal Clinical Nutrition, 78, 370-375.
[179] van Tol, A., Zock, P.L., van Gent, T., Scheek, L.M. and Katan, M. (1995) Dietary Trans Fatty Acids Increase Serum Cholesteryl Ester Transfer Protein Activity in Man. Atherosclerosis, 115, 129-134. 05509-H
[180] Parks, J.S., Huggins, K.W., Gebre, A.K. and Burleson, E.R. (2000) Phosphatidylcholine Fluidity and Structure Affect Lecithin: Cholesterol Acyltransferase Activity. Journal of Lipid Research, 41, 546-553.
[181] Khan, S.A. and Heuvel, J.P.V. (2003) Reviews: Current Topicsrole of Nuclear Receptors in the Regulation of Gene Expression by Dietary Fatty Acids (Review). The Journal of Nutritional Biochemistry, 14, 554-567. 00098-6
[182] Heuvel, J.P.V. (2009) Cardiovascular Disease-Related Genes and Regulation by Diet. Current Atherosclerosis Reports, 11, 448-455.
[183] Heuvel, J.P.V. (2004) Diet, Fatty Acids, and Regulation of Genes Important for Heart Disease. Current Atherosclerosis Reports, 6, 432-440.
[184] Cantó, C., Jiang, L.Q., Deshmukh, A.S., Mataki, C., Coste, A., Lagouge, M., Zierath, J.R., et al. (2010) Interdependence of AMPK and SIRT1 for Metabolic Adaptation to Fasting and Exercise in Skeletal Muscle. Cell Metabolism, 11, 213-219.
[185] Wang, J., Fivecoata, H., Hoa, L., Pana, Y., Linga, E.and Pasinetti, G.M. (2010) The Role of Sirt1: At the Crossroad between Promotion of Longevity and Protection against Alzheimer’s Disease Neuropathology. Biochimica et Biophysica Acta (BBA) , Proteins and Proteomics, 1804, 1690-1694.
[186] Donmez, G., Wang, D., Cohen, D.E. and Guarente, L. (2010) SIRT1 Suppresses Beta-Amyloid Production by Activating the Alpha-Secretase Gene ADAM10. Cell, 142, 320-332.
[187] Xu, F., Gao, Z., Zhang, J., Rivera, C.A., Yin, J., Weng, J., et al. (2010) Lack of SIRT1 (Mammalian Sirtuin 1) Activity Leads to Liver Steatosis in the SIRT1+/﹣ Mice: A Role of Lipid Mobilization and Inflammation. Endocrinology, 151, 2504-2514.
[188] Purushotham, A., Xu, Q. and Li, X. (2012) Systemic SIRT1 Insufficiency Results in Disruption of Energy Homeostasis and Steroid Hormone Metabolism upon High-Fat-Diet Feeding. The FASEB Journal, 26, 656-667.
[189] Martins, I.J., Wilson, A.C., Lim, W.L.F., Laws, S.M., Fuller, S.J. and Martins, R.N. (2012) Sirtuin-1 Mediates the Obesity Induced Risk of Common Degenerative Diseases: Alzheimer’s Disease, Coronary Artery Disease and Type 2 Diabetes. Health, 4, 1448-1456.
[190] Honig, L.S., Tang, M.X., Albert, S., Costa, R., Luchsinger, J., Manly, J., et al. (2003) Stroke and the Risk of Alzheimer Disease. Archives of Neurology, 60, 1707-1712.
[191] Albi, E., Michelli, M. and Magni, M.P.V. (1996) Phospholipids and Nuclear RNA. Cell Biology International, 20, 407-412.
[192] Zhdanov, R.I., Struchkov, V.A., Dyabina, O. and Strazhevskaya, N.B. (2001) Chromatin-Bound Cardiolipin: The Phospholipid of Proliferation.Cytobios, 106, 55-61.
[193] Albi, E. and Magni, M.P.V. (2004) The Role of Intranuclear Lipids. Biology of the Cell, 96, 657-667.
[194] Hunt, A.N. (2006) Dynamic Lipidomics of the Nucleus. Journal of Cellular Biochemistry, 97, 244-251.
[195] Albi, E. and Villani, M. (2009) Nuclear Lipid Microdomains Regulate Cell Function. Communicative & Integrative Biology, 2, 23-24.
[196] Cascianelli, G., Villani, M., Tosti, M., Marini, F., Bartoccini, E., Magni, M.V., et al. (2008) Lipid Microdomains in Cell Nucleus. Molecular Biology of the Cell, 19, 5289-5295.
[197] Bazan, N.G. (2005) Synaptic Signaling by Lipids in the Life and Death of Neurons. Molecular Neurobiology, 31, 219-230.
[198] Pope, S., Land, J.M. and Heales, S.J. (2008) Oxidative Stress and Mitochondrial Dysfunction in Neurodegeneration; Cardiolipin a Critical Target? Biochimica et Biophysica Acta (BBA) , Bioenergetics, 1777, 794-799.
[199] Kirkland, R.A., Adibhatla, R.M., Hatcher, J.F. and Franklin, J.L. (2002) Loss of Cardiolipin and Mitochondria during Programmed Neuronal Death: Evidence of a role for Lipid Peroxidation and Autophagy. Neuroscience, 115, 587-602. 00512-2
[200] Pébay, A., Toutant, M., Prémont, J., Calvo, C.F., Venance, L., Cordier, J., et al. (2001) Sphingosine-1-Phosphate Induces Proliferation of Astrocytes: Regulation by Intracellular Signalling Cascades. European Journal of Neuroscience, 13, 2067-2076.
[201] Lucki, N.C. and Sewer, M.B. (2012) Nuclear Sphingolipid Metabolism. Annual Review of Physiology, 74, 131-151.
[202] Spohr, T.C., Dezonne, R.S., Nones, J., Souza, C., Einicker-Lamas, M., Gomes, F.C.A., et al. (2012) Sphingosine 1-Phosphate-Primed Astrocytes Enhance Differentiation of Neuronal Progenitor Cells. Journal of Neuroscience Research, 90, 1892-902.
[203] Stipursky, J., Spohr, T.C., Sousa, V.O. and Gomes, F.C.A. (2012) Neuron-Astroglial Interactions in Cell-Fate Commitment and Maturation in the Central Nervous System. Neurochemistry Research, 37, 2402-2418.
[204] Buccoliero, R. and Futerman, A.H. (2003) The Roles of Ceramide and Complex Sphingolipids in Neuronal Cell Function. Pharmacology Research, 47, 409-419. 00049-5
[205] Chun-Xia, Y. and Tschöp, M.H. (2012) Brain-Gut-Adipose-Tissue Communication Pathways at a Glance. Disease Models & Mechanisms, 5, 583-587.
[206] Caspi, L., Wang, P.Y and Lam, T.K. (2007) A Balance of Lipid-Sensing Mechanismsin the Brain and Liver. Cell Metabolism, 6, 99-104.
[207] Vacca, M., Degirolamo, C., Mariani-Costantini, R., Palasciano, G. and Moschetta, A. (2011) Lipid-Sensing Nuclear Receptors in the Pathophysiology and Treatment of the Metabolic Syndrome. Wiley Interdisciplinary Reviews: Systems Biology and Medicine, 3, 562-587.
[208] Beaven, S.W. and Tontonoz, P. (2006) Nuclear Receptors in Lipid Metabolism: Targeting the Heart of Dyslipidemia. Annual Review of Medicine, 57, 313-329.
[209] Ferrari, A., Fiorino, E., Giudici, M., Gilardi, F., Galmozzi, A., Mitro, N., et al. (2012) Linking Epigenetics to Lipid Metabolism: Focus on Histone Deacetylases. Molecular Membrane Biology, 29, 257-266.
[210] Goetzl, E.J. (2007) Diverse Pathways for Nuclear Signaling by G Protein-Coupled Receptors and Their Ligands. The FASEB Journal, 21, 638-642.
[211] Alemany, R., Perona, J.S., Sánchez-Dominguez, J.M., Montero, E., Cañizares, J., Bressani, R., Escribá, P.V., et al. (2007) G Protein-Coupled Receptor Systems and Their Lipid Environment in Health Disorders during Aging. Biochimica et Biophysica Acta (BBA, Biomembranes, 1768, 964-975.
[212] Takahashi, T., Kajikawa, Y. and Tsujimoto, T. (1998) G-Protein-Coupled Modulation of Presynaptic Calcium Currents and Transmitter Release by a GABAB Receptor. The Journal of Neuroscience, 18, 3138-3146.
[213] Zamponia, G.W. and Currie, K.P.M. (2013) Regulation of CaV2 Calcium Channels by G Protein Coupled Receptors. Biochimica et Biophysica Acta (BBA, Biomembranes, 1828, 1629-1643.
[214] Riboni, L., Prinetti, A., Bassi, R. and Tettamanti, G. (1994) Formation of Bioactive Sphingoid Molecules from Exogenous Sphingomyelin in Primary Cultures of Neurons and Astrocytes. FEBS Letters, 352, 323-326. 00984-8
[215] Reimertz, C., Reimertz, C., Münstermann, G., Kögel, D. and Prehn, J.H.M. (2002) Ceramide-Induced Apoptosis of D283 Medulloblastoma Cells Requires Mitochondrial Respiratory Chain Activity but Occurs Independently of Caspases and Is Not Sensitive to Bcl-xL Overexpression. Journal of Neurochemistry, 82, 482-494.
[216] Won, J.S, Singh, A.K. and Singh, I. (2007) Lactosylceramide: A Lipid Second Messenger in Neuroinflammatory Disease. Journal of Neurochemistry, 103, 180-191.
[217] Hannun, Y.A. and Obeid, L.M. (2008) Principles of Bioactive Lipid Signalling: Lessons from Sphingolipids. Nature Reviews Molecular Cell Biology, 9, 139-150.
[218] Spiegel, S. and Milstien, S. (2002) Sphingosine 1-Phosphate, a Key Cell Signaling Molecule. The Journal of Biological Chemistry, 277, 25851-25854.
[219] Walter, L., Franklin, A., Witting, A., Möller, T. and Stella, N. (2002) Astrocytes in Culture Produce Anandamide and Other Acylethanolamides. Journal of Biological Chemistry, 277, 20869-20876.
[220] Rao, R.P., Vaidyanathan, N., Rengasamy, M., Oommen, A.M., Somaiya, N. and Jagannath, M.R. (2013) Sphingolipid Metabolic Pathway: An Overview of Major Roles Played in Human Diseases. Journal of Lipids, 2013, Article ID: 178910.
[221] Ariga, T., Jarvis, W.D. and Yu, R.K. (1998) Role of Sphingolipid-Mediated Cell Death in Neurodegenerative Diseases. Journal of Lipid Research, 39, 1-16.
[222] Nishimura, H., Akiyama, T., Irei, I., Hamazaki, S. and Sadahira, Y. (2010) Cellular Localization of Sphingo-sine-1-Phosphate Receptor 1 Expression in the Human Central Nervous System. Journal of Histochemistry Cytochemistry, 58, 847-856.
[223] Burrows, E.L. and Bird, R.J. (2012) Obesity-Associated Steatotic Liver Exhibits Aberrant or Altered Sphingolipid Composition and Preferentially Accumulates Ceramide Species Containing Long Chain Fatty Acids. Health, 4, 1578-1587.
[224] Samad, F., et al. (2006) Altered Adipose and Plasma Sphingolipid Metabolism in Obesity: A Potential Mechanism for Cardiovascular and Metabolic Risk. Diabetes, 55, 2579-2587.
[225] Kowalski, G.M., et al. (2013) Plasma Sphingosine-1-Phosphate Is Elevated in Obesity. PLoS ONE, 8, e72449.
[226] Dinkins, M., He, Q., Zhu, G., Poirier, C., Campbell, A., Mayer-Proschel, M., et al. (2012) Astrocytes Secrete Exosomes Enriched with Proapoptotic Ceramide and Prostate Apoptosis Response 4 (PAR-4) : Potential Mechanism of Apoptosis Induction in Alzheimer Disease (AD).Journal of Biological Chemistry, 287, 21384-21395.
[227] Navarrete, M. and Araque, A. (2008) Endocannabinoids Mediate Neuron-Astrocyte Communication. Neuron, 57, 883-893.
[228] Berghuis, P., Dobszay, M.B., Wang, X., Spano, S., Ledda, F., Sousa, K.M., et al. (2005) Endocannabinoids Regulate Interneuron Migration and Morphogenesis by Transactivating the TrkB Receptor. Proceedings of the National Academy of Sciences of the United States of America, 102, 19115-19120.
[229] Diana, M.A and Bregestovski, P. (2005) Calcium and Endocannabinoids in the Modulation of Inhibitory Synaptic Transmission. Cell Calcium, 37, 497-505.
[230] Kuo, J. and Ikeda, S.R. (2004) Endocannabinoids Modulate N-Type Calcium Channels and G-Protein-Coupled Inwardly Rectifying Potassium Channels via CB1 Cannabinoid Receptors Heterologously Expressed in Mammalian Neurons. Molecular Pharmacology, 65, 665-674.
[231] Bosier, B., Bellocchio, L., Metna-Laurent, M., Soria-Gomez, E., Matias, I., Hebert-Chatelain, E., et al. (2013) Astroglial CB1 Cannabinoid Receptors Regulate Leptin Signalling in Mouse Brain Astrocytes. Molecular Mechanism, 2, 393-404.
[232] Kirkham, T.C. (2009) Cannabinoids and Appetite: Food Craving and Food Pleasure. International Review of Psychiatry, 21, 163-171.
[233] Lichtman, A.H. and Cravatt, B.F. (2005) Food for Thought: Endocannabinoid Modulation of Lipogenesis. The Journal of Clinical Investigation, 115, 1130-1133.
[234] Martins, I.J., et al. (2013) Anti-Oxidative Acyl CoA Cholesterol Acyltransferase Inhibitor AVASIMIBE Reduces the Impact of a High Cholesterol Diet on Brain Lipid Peroxidation in Mice. ADPD2013, Florence.
[235] Petrosillo, P., Portincasab, P., Grattaglianob, I., Casanovaa, G., Materaa, M., Ruggiero, F.M., et al. (2007) Mitochondrial Dysfunction in Rat with Nonalcoholic Fatty Liver: Involvement of Complex I, Reactive Oxygen Species and Cardiolipin. Biochimica Biophysica Acta (BBA), Bioenergetics, 1767, 1260-1267.
[236] Sparagna, G.C., Chicco, A.J., Murphy, R.C., Bristow, M.R., Johnson, C.A., Rees, M.L., et al. (2007) Loss of Cardiac Tetralinoleoyl Cardiolipin in Human and Experimental Heart Failure. The Journal of Lipid Research, 48, 1559-1570.
[237] Han, X., Yang, J., Yang, K., Zhao, Z., Abendschein, D.R. and Gross, R.W. (2007) Alterations in Myocardial Cardiolipin Content and Composition Occur at the Very Earliest Stages of Diabetes: A Shotgun Lipidomics Study. Biochemistry, 46, 6417-6428.
[238] Paradies, G., Petrosillo, G., Paradies, V. and Ruggiero, F.M. (2011) Mitochondrial Dysfunction in Brain Aging: Role of Oxidative Stress and Cardiolipin. Neurochemistry International, 58, 447-457.
[239] Wiswedel, I., Gardemann, A., Storch, A., Peter, D. and Schild, L. (2010) Degradation of Phospholipids by Oxidative Stress—Exceptional Significance of Cardiolipin. Free Radical Research, 44, 135-145.
[240] Demuro, A., Smith, M. and Parker, I. (2011) Single-Channel Ca2+ Imaging Implicates Aβ1-42 Amyloid Pores in Alzheimer’s Disease Pathology. Journal of Cell Biology, 195, 515-524.
[241] Short, B. (2011) Imaging β Amyloid’s Pore Performance: Study Visualizes Alzheimer’s Disease-Related Peptides Forming Toxic Calcium Channels in the Plasma Membrane. Journal of Cell Biology, 195, 345.
[242] Walsh, P. and Sharpe, S. (2011) Structure-Toxicity Relationships of Amyloid Peptide Oligomers. In: Chang, R.C.C, Ed., Advanced Understanding of Neurodegenerative Diseases, InTech, Rijeka, Chapter 4.
[243] Merril, A.H. (1999) Regulation of Cytochrome P450 Expression by Sphingolipids. Chemistry and Physics Lipids, 102, 131-139. 00081-X
[244] Kim, Y.M., Park, T.S and Kim, S.G. (2013) The Role of Sphingolipids in Drug Metabolism and Transport. Expert Opinion on Drug Metabolic &Toxicology, 9, 319-331.
[245] Osindea, M., Mullershausenb, F. and Deva, K.K. (2007) Phosphorylated FTY720 Stimulates ERK Phosphorylation in Astrocytes via S1P Receptors. Neuropharmacology, 52, 1210-1218.
[246] Bradley, S.J. and Challiss, R.A. (2012) G Protein-Coupled Receptor Signalling in Astrocytes in Health and Disease: A Focus on Metabotropic Glutamate Receptors. Biochemistry Pharmacology, 84, 249-259.
[247] Vassart, G.and Costagliola, S. (2011) G Protein-Coupled Receptors: Mutations and Endocrine Diseases. Nature Review Endocrinology, 7, 362-372.
[248] Gobeil, F., Fortier, A., Zhu, T., Bossolasco, M., Leduc, M., Grandbois, M., et al. (2006) G-Protein-Coupled Receptors Signalling at the Cell Nucleus: An Emerging Paradigm. Canadian Journal of Physiology Pharmacology, 84, 287-297.
[249] Erol, A. (2008) An Integrated and Unifying Hypothesis for the Metabolic Basis of Sporadic Alzheimer’s Disease. Journal of Alzheimer’s Disease, 13, 241-253.
[250] Hsuchou, H., He, Y., Kastin, A.J., Tu, H., Markadakis, E.N., Rogers, R.C., et al. (2009) Obesity Induces Functional Astrocytic Leptin Receptors in Hypothalamus. Brain, 132, 889-902.
[251] Chowen, J.A., Argente, J. and Horvath, T.L. (2013) Uncovering Novel Roles of Nonneuronal Cells in Body Weight Homeostasis and Obesity. Endocrinology, 154, 3001-3007.
[252] García-Cáceres, C., Fuente-Martín, E., Argente, J.and Chowen, J.A. (2012) Emerging Role of Glial Cells in the Control of Body Weight. Molecular Metabolism, 1, 37-46.
[253] Lee, E.B. and Ahima, R.S. (2012) Alteration of Hypothalamic Cellular Dynamics in Obesity. The Journal of Clinical Investigation, 122, 22-25.
[254] Levin, B.E., Magnan, C., Dunn-Meynell, A. and Le Foll, C. (2011) Metabolic Sensing and the Brain: Who, What, Where, and How? Endocrinology, 152, 2552-2557.
[255] García-Cáceres, C., Yi, C.X. and Tschöp, M.H. (2013) Hypothalamic Astrocytes in Obesity. Endocrinology and Metabolism Clinical of North America, 42, 57-66.
[256] Fuente-Martín, E., García-Cáceres, C., Granado, M., de Ceballos, M.L., Sánchez-Garrido, M.á., Sarman, B., et al. (2012) Leptin Regulates Glutamate and Glucose Transporters in Hypothalamic Astrocytes. The Journal of Clinical Investigation, 122, 3900-3913.
[257] Sheridan, P.A. (2010) Obesity and Microglial Activation: Potential for Synergism in Neurodegenerative Diseases. The FASEB Journal (Meeting Abstract Supplement), 326, 24.
[258] Thaler, J.P., et al. (2011) Rapid Onset of Hypothalamic Inflammation, Reactive Gliosis and Microglial Accumulation during High-Fat Diet-Induced Obesity. Endocrinology Review, 32.
[259] Yi, C.X., Al-Massadia, O., Donelana, E., Lehtia, M., Webera, J., Ress, C., et al. (2012) Exercise Protects against High-Fat Diet-Induced Hypothalamic Inflammation. Physiology & Behavior, 106, 485-490.
[260] Buckmana, L.B., Hasty, A.H., Flaherty, D.K., Buckman, C.T., Thompson, M.M., Matlock, B.K., et al. (2014) High-Fat Diet Induced Obesity Is Associated with CNS Recruitment of Monocytes with the Phenotype of Activated Microglia/Macrophage. Brain Behaviour and Immunity, 35, 33-42.
[261] Camargo N., Brouwers, J.F., Loos, M., Gutmann, D.H., Smit, A.B. and Verheijen, M.H.G. (2012) High-Fat Diet Ameliorates Neurological Deficits Caused by Defective Astrocyte Lipid Metabolism. TheFASEB Journal, 26, 4302-4315.
[262] Moraes, J.C., Coope, A., Morari, J., Cintra, D.E., Roman, E.A., Pauli, J.R., et al. (2009) High-Fat Diet Induces Apoptosis of Hypothalamic Neurons. PLoS ONE, 4, e5045.
[263] Gandhi G.K., Ball, K.K., Cruz, N.F. and Dienel, G.A. (2010) Hyperglycaemia and Diabetes Impair Gap Junctional Communication among Astrocytes. ASN Neurology, 2, e00030.
[264] Coleman, E.S., Dennisa, J.C., Bradena, T.D., Judda, R.L. and Posner, P. (2010) Insulin Treatment Prevents Diabetes-Induced Alterations Inastrocyte Glutamate Uptake and GFAP Content in Rats at 4 and 8Weeks of Diabetes Duration. Brain Research, 1306, 131-141.
[265] Muranyi, M., Ding, C., He, Q.P., Lin, Y. and Li, P.A. (2006) Streptozotocin-Induced Diabetes Causes Astrocyte Death after Ischemia and Reperfusion Injury. Diabetes, 55, 349-355.
[266] Montgomery, D.L. (1994) Astrocytes: Form, Functions, and Roles in Disease.Veterinary Pathology, 31, 145-167.
[267] Garcia-Segura, L.M., Chowen, J.A. and Naftolin, F. (1996) Endocrine Glia: Roles of Glial Cells in the Brain Actions of Steroid and Thyroid Hormones and in the Regulation of Hormone Secretion. Frontiers in Neuroendocrinology, 17, 180-211.
[268] Theodosis, D.T., Piet, R., Poulain, D.A. and Oliet, S.H.R. (2004) Neuronal, Glial and Synaptic Remodeling in the Adult Hypothalamus: Functional Consequences and Role of Cell Surface and Extracellular Matrix Adhesion Molecules. Neurochemistry International, 45, 491-501.
[269] Horvath, T.L., Sarmana, B., García-Cáceresd, C., Enriorie, P.J., Sotonyia, P., Shanabrough, M., et al. (2010) Synaptic Input Organization of the Melanocortin System Predicts Diet-Induced Hypothalamic Reactive Gliosis and Obesity. Proceedings of the National Academy of Sciences of the United States of America, 107, 14875-14880.
[270] Thaler, J.P., Yi, C.X., Schur, E.A., Guyenet, S.J., Hwang, B.H., Dietrich, M.O., et al. (2012) Obesity Is Associated with Hypothalamic Injury in Rodents and Humans. The Journal of Clinical Investigation, 122, 153-162.
[271] Yi, C.X., Habegger, K.M., Chowen, J.A., Stern J. and Tschöp, M.H. (2011) A Role for Astrocytes in the Central Control of Metabolism. Neuroendocrinology, 93, 143-149.
[272] Sundvall, J., Saltevo, J., Niskanen, L., Kautiainen, H., Teittinen, J., Oksa, H., et al. (2011) Serum Calcium Level Is Associated with Metabolic Syndrome in the General Population: FIN-D2D Study. European Journal of Endocrinology, 165, 429-434.
[273] Sun, G., Vasdev, S., Martin, G.R., Gadag, V. and Zhang, H. (2005) Altered Calcium Homeostasis Is Correlated with Abnormalities of Fasting Serum Glucose, Insulin Resistance, and Beta-Cell Function in the Newfoundland Population. Diabetes, 51, 3336-3339.
[274] Hagström, E., Hellman, P., Lundgren, E., Lind, L. and Ärnlöv, J. (2007) Serum Calcium Is Independently Associated with Insulin Sensitivity Measured with Euglycaemic-Hyperinsulinaemic Clamp in a Community-Based Cohort. Diabetologia, 50, 317-324.
[275] Santos, L.C.D., Cintra, I.D.P., Fisberg, M. and Martini, L.A. (2008) Calcium Intake and Its Relationship with Adiposity and Insulin Resistance in Post-Pubertal Adolescents. Journal of Human Nutrition and Dietetics, 21, 109-116.
[276] Draznin, B. (1993) Cytosolic Calcium and Insulin Resistance. American Journal of Kidney Diseases, 21, S32-S38. 70122-F
[277] Wang, X., Takano, T. and Nedergaard, M. (2009) Astrocytic Calcium Signaling: Mechanism and Implications for Functional Brain Imaging. Methods Molecular Biology, 489, 93-109.
[278] Dejeansa, N., Tajeddine, N., Beck, R., Verrax, J., Taper, H., Gailly, P., et al. (2010) Endoplasmic Reticulum Calcium Release Potentiates the ER Stress and Cell Death Caused by an Oxidative Stress in MCF-7 Cells. Biochemical Pharmacology, 79, 1221-1230.
[279] Hammadi, M., Oulidi, A., Gackière, F., Katsogiannou, M., Slomianny, C., Roudbaraki, M., et al. (2013) Modulation of ER Stress and Apoptosis by Endoplasmic Reticulum Calcium Leak via Translocon during Unfolded Protein Response: Involvement of GRP78. The FASEB Journal, 27, 1600-1609.
[280] Schönthal, A.H. (2012) Endoplasmic Reticulum Stress: Its Role in Disease and Novel Prospects for Therapy. Scientifica (Cairo), 2012, Article ID: 857516.
[281] Xu, C., Bailly-Maitre, B. and Reed, J.C. (2005) Endoplasmic Reticulum Stress: Cell Life and Death Decisions. The Journal of Clinical Investigation, 115, 2656-2664.
[282] Fu, S., Yang, L., Li, P., Hofmann, O., Dicker, L., Hide, W., et al. (2011) Aberrant Lipid Metabolism Disrupts Calcium Homeostasis Causing Liver Endoplasmic Reticulum Stress in Obesity. Nature, 473, 528-531.
[283] Högback, S., Leppimäki, P., Rudnäs, B., Björklund, S., Slotte, J.P. and Törnquist, K. (2003) Ceramide 1-Phosphate Increases Intracellular Free Calcium Concentrations in thyroid FRTL-5 Cells: Evidence for an Effect Mediated by Inositol 1, 4, 5-Trisphosphate and Intracellular Sphingosine 1-Phosphate. Biochemical Journal, 370, 111-119.
[284] Kobrinsky, E., Spielman, A.I., Rosenzweig, S. and Marks, A.R. (1999) Ceramide Triggers Intracellular Calcium Release via the IP(3) Receptor in Xenopus laevis Oocytes. American Journal of Physiology, 277, C665-C672.
[285] Darios, F., Muriel, M.P., Khondiker, M.E., Brice, A. and Ruberg, M. (2005) Neurotoxic Calcium Transfer from Endoplasmic Reticulumto Mitochondria Is Regulated by Cyclin-Dependent Kinase5-Dependent Phosphorylation of Tau. The Journal of Neuroscience, 25, 4159-4168.
[286] Sergeeva, M., Strokin, M. and Reiser, G. (2005) Regulation of Intracellular Calcium Levels by Polyunsaturated Fatty Acids, Arachidonic Acid and Docosahexaenoic Acid, in Astrocytes: Possible Involvement of Phospholipase A2. Reproduction Nutrition Development, 45, 633-646.
[287] Bonin, A. and Khan, N.A. (2000) Regulation of Calcium Signalling by Docosahexaenoic Acid in Human T-Cells. Implication of CRAC Channels. Journal of Lipid Research, 41, 277-284.
[288] Vreugdenhil, M., Bruehl, C., Voskuyl, R.A., Kang, J.X., Leaf, A. and Wadman, W.J. (1996) Polyunsaturated Fatty Acids Modulate Sodium and Calcium Currentsin CA1 Neurons. Proceedings of the National Academy of Sciences of the United States of America, 93, 12339-12365.
[289] Venable, M.E., Zimmerman, G.A., McIntyre, T.M. and Prescott, S.M. (1993) Platelet-Activating Factor: A Phospholipid Autacoid with Diverse Actions. Journal of Lipid Research, 34, 691-702.
[290] Bazan, N.G. (1993) The Neuromessenger Platelet-Activating Factor in Plasticity and Neurodegeneration. Progress in Brain Research, 118, 281-291. 63215-X
[291] Kudolo, G.B., Bressler, P. and DeFronzo, R.A. (1997) Plasma PAF Acetylhydrolase in Non-Insulin Dependent Diabetes Mellitus and Obesity: Effect of Hyperinsulinemia and Lovastatin Treatment. Journal of Lipid Mediator and Cell Signalling, 17, 97-113. 00023-0
[292] Matsubara, S.M., Maruoka, S. and Katayose, S. (2002) Inverse Relationship between Plasma Adiponectin and Leptin Concentrations in Normal-Weight and Obese Women.European Journal of Endocrinology, 147, 173-180.
[293] Ybarra, Y., Doñate, T., Jurado, J. and Pou, J.M. (2007) Primary Hyperparathyroidism, Insulin Resistance and Cardiovascular Disease. A Review. Nursing Clinics of North America, 42, 79-85.
[294] Lee, E.B., Warmann, G., Dhir, R. and Ahima, R.S. (2011) Metabolic Dysfunction Associated with Adiponectin Deficiency Enhances Kainic Acid-Induced Seizure Severity. The Journal of Neuroscience, 31, 14361-14366.
[295] Dezonne, R.S., Stipursky, J., Araujo, A.P., Nones, J., Pavão, M.S., Porcionatto, M., et al. (2013) Thyroid Hormone Treated Astrocytes Induce Maturation of Cerebral Cortical Neurons through Modulation of Proteoglycan Levels. Frontiers in Cell Neuroscience, 7, 125.
[296] Trentin, A.G. (2006) Thyroid Hormone and Astrocyte Morphogenesis. Journal of Endocrinology, 189, 189-197.
[297] Calzà, L. (2007) Thyroid Hormone Regulation of Neural and Oligodendrocyte Precursors in the Mature Brain: A Possibility for Remyelination and Neuroprotection. Endocrine Abstracts, 14, S2.
[298] Perello, M. and Raingo, J. (2013) Leptin Activates Oxytocin Neurons of the Hypothalamic Paraventricular Nucleus in Both Control and Diet-Induced Obese Rodents. PLoS ONE, 8, e59625.
[299] Velmurugan, S., Russell, J.A. and Leng, G. (2013) Systemic Leptin Increases the Electrical Activity of Supraoptic Nucleus Oxytocin Neurones in Virgin and Late Pregnant Rats. Journal of Neuroendocrinology, 25, 383-390.
[300] Hoyda, T.D., Fry, M., Ahima, R.S. and Ferguson, A.V. (2007) Adiponectin Selectively Inhibits Oxytocin Neurons of the Paraventricular Nucleus of the Hypothalamus. Journal of Physiology, 585, 805-816.
[301] Ciosek, J. and Drobnik, J. (2004) Vasopressin and Oxytocin Release and the Thyroid Function. Journal of Physiology Pharmacology, 55, 423-441.
[302] Betsy, A., Binitha, M.P. and Sarita, S. (2013) Zinc Deficiency Associated with Hypothyroidism: An Overlooked Cause of Severe Alopecia. International Journal of Trichology, 5, 40-42.
[303] Gee, J.R. and Keller, J.N. (2005) Astrocytes: Regulation of Brain Homeostasis via Apolipoprotein E. International Journal of Biochemistry Cell Biology, 37, 1145-1150.
[304] Zhao, Z. and Michaely, P. (2009) The Role of Calcium in Lipoprotein Release by the Low-Density Lipoprotein Receptor. Biochemistry, 48, 7313-7324.
[305] Mulder, M., Koopmansb, G., Wassinkb, G., Al Mansourib, G., Simardb, M.L., Havekes, L.M., et al. (2007) LDL Receptor Deficiency Results in Decreased Cell Proliferation and Presynaptic Bouton Density in the Murine Hippocampus. Neuroscience Research, 59, 251-256.
[306] Faux, C.H. and Parnavela, J.G. (2007) The Role of Intracellular Calcium and RhoA in Neuronal Migration. Science’s Signal Transduction Knowledge Environment, 2007, pe62.
[307] Rakic, P. and Komuro, H. (1995) The Role of Receptor/Channel Activity in Neuronal Cell Migration. Journal of Neurobiology, 26, 299-315.
[308] Berger, M.J. (1998) Neuronal Calcium Signaling. Neuron, 21, 13-26. 80510-3
[309] Rosenberg, S.S. and Spitzer, N.C. (2011) Calcium Signaling in Neuronal Development. Cold Spring Harbour Perspective in Biology, 3, a004259.
[310] Fadeel, B. and Xue, D. (2009) The Ins and Outs of Phospholipid Asymmetry in the Plasma Membrane: Roles in Health and Disease. Critical Reviews in Biochemistry and Molecular Biology, 44, 264-277.
[311] Barenholz, Y. (2004) Sphingomyelin and Cholesterol: From Membrane Biophysics and Rafts to Potential Medical Applications. Subcellular Biochemistry, 37, 167-215.
[312] Viani, P., Cervato, G., Marchesini, S. and Cestaro, B. (1986) Fluorospectroscopic Studies of Mixtures of Distearoylphosphatidylcholine and Sulfatides with Defined Fatty Acid Compositions. Chemistry and Physics Lipids, 39, 41-51. 90098-8
[313] Nybond, S., Björkqvist, J., Slotte, J.P. and Ramstedt, B. (2007) Sulfatide Exhibits Calcium Dependent Stabilization of Sphingomyelin/Cholesterol Domains in Bilayer Membranes. Chemistry and Physics of Lipids, 149, S36.
[314] Han, X., Holtzman, D.M., McKeel Jr., D.W., Kelley, J. and Morris, J.C. (2002) Substantial Sulfatide Deficiency and Ceramide Elevation in Very Early Alzheimer’s Disease: Potential Role in Disease Pathogenesis. Journal of Neurochemistry, 82, 809-818.
[315] Han, X., Cheng, H., Fryer, J.D., Fagan, A.M. and Holtzman, D.M. (2003) Novel Role for Apolipoprotein E in the Central Nervous System. Modulation of Sulfatide Content. Journal of Biological Chemistry, 278, 8043-8051.
[316] Berntson, Z., Hansson, E., Rönnbäck, L. and Fredman, P. (1998) Intracellular Sulfatide Expression in a Subpopulation of Astrocytes in Primary Cultures. Journal of Neuroscience Research, 52, 559-568. 1097-4547(19980601) 52:5<559::AID-JNR8>3.0.CO;2-B
[317] Takahashi, T and Suzuki, T. (2012) Role of Sulfatide in Normal and Pathological Cells and Tissues. Journal of Lipid Research, 53, 1437-1450.
[318] Zeng, Y and Han, X. (2008) Sulfatides Facilitate Apolipoprotein E-Mediated Amyloid-β Peptideclearance through an Endocytotic Pathway. Journal of Neurochemistry, 106, 1275-1286.
[319] Buschard, K., Høy, M., Bokvist, K., Olsen, H.L., Madsbad, S., Fredman, P., et al. (2002) Sulphatide Controls Insulin Secretion by Modulation of ATP-Sensitive K+-Channel Activity and Ca2+-Dependent Exocytosis in Rat Pancreatic Beta-Cells. Diabetes, 51, 2514-2521.
[320] Chi, S. and Qi, Z. (2006) Regulatory Effect of Sulphatides on BKCa Channels. British Journal of Pharmacology, 149, 1031-1038.
[321] Kim, W.T., Rioult, M.G. and Cornell-Bell, A.H. (1994) Glutamate-Induced Calcium Signaling in Astrocytes.Glia, 11, 173-184.
[322] Yagi, K., Onaka, T. and Yoshida, A. (1998) Role of NMDA Receptors in the Emotional Memory Associated with Neuroendocrine Responses to Conditioned Fear Stimuli in the Rat. Neuroscience Research, 30, 279-286. 00008-X
[323] Talantovaa, M., Sanz-Blasco, S., Zhang, X., Xia, P., Akhtar, M.W., Okamoto, S., et al. (2013) Aβ Induces Astrocytic Glutamate Release, Extrasynaptic NMDA Receptor Activation, and Synaptic Loss. Proceedings of the National Academy of Sciences of the United States of America, Early Edition.
[324] Parpura, V. and Haydon, P.G. (2000) Physiological Astrocytic Calcium Levels Stimulate Glutamate Release to Modulate Adjacent Neurons. Proceedings of the National Academy of Sciences of the United States of America, 97, 8629-8634.
[325] Randal, R.B. and Thayer, S.A. (1992) Glutamate-Induced Calcium Transient Triggers Delayed Calcium Overload and Neurotoxicity in Rat Hippocampal Neurons. The Journal of Neuroscience, 12, 1882-l895.
[326] Lipton, S.A. and Nicotera, P. (1998) Calcium, Free Radicals and Excitotoxins in Neuronal Apoptosis. Cell Calcium, 23, 165-171. 90115-4
[327] Kessels, H.W., Nabavi, S. and Malinow, R. (2013) Metabotropic NMDA Receptor Function Is Required for β-Amyloid-Induced Synaptic Depression. Proceedings of the National Academy of Sciences of the United States of America, 110, 4033-4038.
[328] Zipfel, G.F. (2000) Neuronal Apoptosis after CNS Injury: The Roles of Glutamate and Calcium. Journal of Neurotrauma, 17, 857-869.
[329] Butche, A.J., Torrecilla, I., Young, K.W., Kong, K.C., Mistry, S.C., Bottrill, A.R., et al. (2009) N-Methyl-D-aspartate Receptors Mediate the Phosphorylation and Desensitization of Muscarinic Receptors in Cerebellar Granule Neurons. The Journal of Biological Chemistry, 284, 17147-17156.
[330] Lu, W.Y., Xiong, Z.G., Lei, S., Orser, B.A., Dudek, E., Browning, M.D., et al. (1999) G-Protein-Coupled Receptors Act via Protein Kinase C and Src to Regulate NMDA Receptors. Nature Neuroscience, 2, 331-338.
[331] Lee, F.S. (2003) Novel Crosstalk between G Protein-Coupled Receptors and NMDA Receptors. Experimental Neurology, 183, 269-272. 00249-8
[332] Qiu, Z., Crutcherb, K.A., Hymana, B.T. and Rebeck, G.W. (2003) ApoE Isoforms Affect Neuronal N-methyl-D-as-partate Calcium Responses and Toxicity via Receptor-Mediated Processes. Neuroscience, 122, 291-303.
[333] Caruso, S., Agnello, C., Campo, M.G. and Nicoletti, F. (1993) Oxytocin Reduces the Activity of N-methyl-D-aspartate Receptors in Cultured Neurons. Journal of Endocrinology Investigation, 16, 921-924.
[334] Brayne, C., Gao, L. and Matthews, F. (2005) Challenges in the Epidemiological Investigation of the Relationships between Physical Activity, Obesity, Diabetes, Dementia and Depression. Neurobiology of Aging, 26, 6-10.
[335] Convit, A. (2005) Links between Cognitive Impairment in Insulin Resistance: An Explanatory Model. Neurobiology of Aging, 26, 31-35.
[336] Greenwood, C.E. and Winocur, G. (2005) High-Fat Diets, Insulin Resistance and Declining Cognitive Function. Neurobiology of Aging, 26, 42-45.
[337] Brand-Miller, J., Hayne, S., Petocz, P. and Colagiuri, S. (2003) Low-Glycemic Index Diets in the Management of Diabetes: A Meta-Analysis of Randomized Controlled Trials. Diabetes Care, 26, 2261-2267.
[338] Brand-Miller, J.C. (2003) Glycemic Load and Chronic Disease. Nutrition Reviews, 61, S49-S55.
[339] Dosunmu, R., Wu, J., Basha, R. and Zawia, N.H. (2007) Environmental and Dietary Risk Factors in Alzheimer’s Disease. Expert Review of Neurotherapeutics, 7, 887-900.
[340] Schiepers, O.J., de Groot, R.H.M., Jolles, J. van Boxtel, M.P.J. (2010) Fish Consumption, Not Fatty Acid Status, Is Related to Quality of Life in a Healthy Population. Prostaglandins, Leukotrienes and Essential Fatty Acids, 83, 31-35.
[341] Horrocks, L.A. and Farooqui, A.A. (2004) Docosahexaenoic Acid in the Diet: Its Importance in Maintenance and Restoration of Neural Membrane Function. Prostaglandins, Leukotrienes and Essential Fatty Acids, 70, 361-372.
[342] Montuschi, P., Barnes, P. and Roberts2nd, L.J. (2007) Insights into Oxidative Stress: The Isoprostanes. Current Medicine Chemistry, 14, 703-717.
[343] Oster, T. and Pillot, T. (2010) Docosahexaenoic Acid and Synaptic Protection in Alzheimer’s Disease Mice. Biochimica Biophysica Acta (BBA), Molecular and Cell Biology of Lipids, 1801, 791-798.
[344] Simopoulos, A.P. (2008) The Importance of the Omega-6/Omega-3 Fatty Acid Ratio in Cardiovascular Disease and Other Chronic Diseases. Experimental Biology Medicine (Maywood), 233, 674-688.
[345] Davidson, M.H. (2006) Mechanisms for the Hypotriglyceridemic Effect of Marine Omega-3 Fatty Acids. American Journal of Cardiology, 98, 27-33.
[346] Denechaud, P.D., Dentin, R., Girard, J. and Postic, C. (2008) Role of ChREBP in Hepatic Steatosis and Insulin Resistance. FEBS Letters, 582, 68-73.
[347] Brisson, C.D. and Andrew, R.D. (2012) A Neuronal Population in Hypothalamus That Dramatically Resists Acute Ischemic Injury Compared to Neocortex. Journal of Neurophysiology, 108, 419-430.
[348] Radak, D., Resanovic, I. and Isenovic, E.R. (2013) Changes in Hypothalamus-Pituitary-Adrenal Axis Following Transient Ischemic Attack. Angiology, Epub Ahead of Print.
[349] Larsson, S.C, Orsini, N. and Wolk, A. (2013) Dietary Calcium Intake and Risk of Stroke: A Dose-Response Meta-Analysis. The American Journal of Clinical Nutrition, 97, 951-957.
[350] Li, K., Kaaks, R., Linseisen, J. and Rohrmann, S. (2012) Associations of Dietary Calcium Intake and Calcium Supplementation with Myocardial Infarction and Stroke Risk and Overall Cardiovascular Mortality in the Heidelberg Cohort of the European Prospective Investigation into Cancer and Nutrition Study (EPIC-Heidelberg). Heart, 98, 920-925.
[351] Heaney, R.P. and Barger-Lux, M.J. (1994) Low Calcium Intake: The Culprit in Many Chronic Diseases. Journal of Dairy Science, 77, 1155-1160. 77052-1
[352] Nones, J., Stipursky, J., Costa, S.L. and Gomes, F.C.A. (2010) Flavonoids and Astrocytes Crosstalking: Implications for Brain Development and Pathology. Neurochemistry Research, 35, 955-996.
[353] Sharma, V., Mishra, M., Ghosh, S., Tewari, R., Basu, A., Seth, P., et al. (2007) Modulation of Interleukin-1β Mediated Inflammatory Response in Human Astrocytes by Flavonoids: Implications in Neuroprotection. Brain Research Bulletin, 73, 55-63.
[354] Silva, A.R., Pinheiro, A.M., Souza, C.S., Freitas, S.R.V.B., Vasconcellos, V., Freire, S.M., et al. (2008) The Flavonoid Rutin Induces Astrocyte and Microglia Activation and Regulates TNF-Alpha and NO Release in Primary Glial Cell Cultures. Cell Biology Toxicology, 24, 75-86.
[355] Xu, S.L., Bi, C.W., Choi, R.C., Zhu, K.Y., Miernisha, A., Dong, T.T., et al. (2013) Flavonoids Induce the Synthesis and Secretion of Neurotrophic Factors in Cultured Rat Astrocytes: A Signaling Response Mediated by Estrogen Receptor. Evidence-Based Complementary and Alternative Medicine, 2013, Article ID127075.
[356] Martins, I.J. and Fernando, W.M.A.D.B. (2014) High Fibre Diets and Alzheimer’s Disease.Food and Nutrition Sciences (Diet and Disease), 5, 410-424.
[357] Ono, K., Yoshiike, Y., Takashima, A, Hasegawa, K., Naiki, H. and Yamada, M. (2003) Potent Anti-Amyloidogenic and Fibril-Destabilizing Effects of Polyphenols in Vitro: Implications for the Prevention and Therapeutics of Alzheimer’s Disease. Journal of Neurochemistry, 87, 172-181.
[358] Choi, Y.J., Kim, T.D., Paik, S.R., Jeong, K.J. and Jung, S.H. (2008) Molecular Simulations for Anti-Amyloidogenic Effect of Flavonoid Myricetin Exerted against Alzheimer’s β-Amyloid Fibrils Formation. Bulletin of the Korean Chemistry Society, 29, 1505-1509.
[359] Hu, Y., Yang, Y., Yu, Y., Wen, G., Shang, N., Zhuang, W., et al. (2013) Synthesis and Identification of New Flavonoids Targeting Liver X Receptor β Involved Pathway as Potential Facilitators of Aβ Clearance with Reduced Lipid Accumulation. Journal of Medicinal Chemistry, 56, 6033-6053.
[360] Jin, C.H., Shin, E.J., Park, J.B., Jang, C.G., Li, Z., Kim, M.S., et al. (2009) Fustin Flavonoid Attenuates Beta-Amyloid (1-42) -Induced Learning Impairment. Journal of Neuroscience Research, 87, 3658-3670.
[361] Jadeja, R.N. and Devkar, R.V. (2014) Polyphenols in Human Health and Disease. Polyphenols in Chronic Diseases and their Mechanisms of Action. Chapter 47, Polyphenols and Flavonoids in Controlling Non-Alcoholic Steatohepatitis, 1, 615-623.
[362] Zhang, S., Zheng, L., Dong, D., Xu, L., Yin, L., Qi, Y., et al. (2013) Effects of Flavonoids from Rosa laevigata Michx Fruit against High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Rats. Food Chemistry, 141, 2108-2116.
[363] Phachonpai, W., Wattanathorn, J., Muchimapura, S., Tong-Un, T. and Preechagoon, D. (2010) Neuroprotective Effect of Quercetin Encapsulated Liposomes: A Novel Therapeutic Strategy against Alzheimer’s Disease. American Journal of Applied Sciences, 7, 480-485.
[364] Cassidy, A., Rimm, E.B., O’Reilly, é.J., Logroscino, G., Kay, C., Chiuve, S.E., et al. (2012) Dietary Flavonoids and Risk of Stroke in Women. Stroke, 43, 946-951.
[365] Sriraksa, N., Wattanathorn, J., Muchimapura, S., Tiamkao, S., Brown, K. and Chaisiwamongkol, K. (2012 ) Cognitive-Enhancing Effect of Quercetin in a Rat Model of Parkinson’s Disease Induced by 6-Hydroxydopamine.Evidence-Based Complementary and Alternative Medicine, 2012, Article ID: 823206.
[366] Horáková, L. (2011) Flavonoids in Prevention of Diseases with Respect to Modulation of Ca-Pump Function. Interdisciplinary Toxicology, 4, 114-124.
[367] van der Heide, D., Kastelijn, J. and Schrödervan der Elst, J.P. (2003) Flavonoids and Thyroid Disease. BioFactors, 19, 113-119.
[368] Santos, M.C., Gonçalves, C.F.L., Vaisman, M., Ferreira, A.C.F. and de Carvalho, D.P. (2011) Impact of Flavonoids on Thyroid Function. Food and Chemical Toxicology, 49, 2495-5012.
[369] Giuliani, C., et al. (2013) The Flavonoid Quercetin Inhibits Thyroid Function in Rats. Endocrinology Review, 34.
[370] Giuliani, C., Noguchi, Y., Harii, N., Napolitano, G., Tatone, D., Bucci, I., et al. (2008) The Flavonoid Quercetin Regulates Growth and Gene Expression in Rat FRTL-5 Thyroid Cells. Endocrinology, 149, 84-92.
[371] Soleas, G.J. (1998) Quercetin and p-Coumaric Acid Concentrations in Commercial Wines. American Journal of Enology and Viticulture, 49, 142-115.
[372] Squizzato A., Gerdes, V.E.A., Brandjes, D.P.M., Büller, H.R. and Stam, J. (2005) Thyroid Diseases and Cerebrovascular Disease. Stroke, 36, 2302-2310.
[373] Baker, D.M. (2007) Thyroid Diseases and Stroke. In: Baker, D.M., Ed., Stroke Prevention in Clinical Practice, Springer, London, 113-114.
[374] Mafrica, F. and Fodale, V. (2008) Thyroid Function, Alzheimer’s Disease and Postoperative Cognitive Dysfunction: A Tale of Dangerous Liaisons? Journal of Alzheimer’s Disease, 14, 95-105.
[375] Franco, M., Chávez, E. and Pérez-Méndez, O. (2011) Pleiotropic Effects of Thyroid Hormones: Learning from Hypothyroidism. Journal of Thyroid Research, 2011, Article ID: 321030.
[376] Davis, P.J., Davis, F.B. and Mousa, S.A. (2009) Thyroid Hormone-Induced Angiogenesis. Current Cardiology Review, 5, 12-16.
[377] Christmann, M. and Kaina, B. (2013) Transcriptional Regulation of Human DNA Repairgenes Following Genotoxic Stress: Trigger Mechanisms, Inducible Responses and Genotoxic Adaptation. Nucleic Acids Research, 41, 8403-8420.
[378] Jalili, M., Pati, S., Rath, B., Bjørklund, G. and Singh, R.B. (2013) Effect of Diet and Nutrients on Molecular Mechanism of Gene Expression Mediated by Nuclear Receptor and Epigenetic Modulation. The Open Nutraceuticals Journal, 6, 27-34.
[379] Pardee, K., Necakov, A.S. and Krause, H. (2011) Nuclear Receptors: Small Molecule Sensors That Coordinate Growth, Metabolism and Reproduction. Subcellular Biochemistry, 52, 123-153.
[380] Petegnief, V. and Planas, A.M. (2013) SIRT1 Regulation Modulates Stroke Outcome. Translational Stroke Research, 4, 663-671.
[381] Clark, D., Tuor, U.I., Thompson, R., Institoris, A., Kulynych, A., Zhang, X., et al. (2012) Protection against Recurrent Stroke with Resveratrol: Endothelial Protection. PLoS ONE, 7, e47792.
[382] Brown, B.M., Peiffer, J.J., Sohrabi, H.R., Mondal, A., Gupta, V.B., Rainey-Smith, S.R., et al. (2012) Intense Physical Activity Is Associated with Cognitive Performance in the Elderly. Translational Psychiatry, 2, e191.

comments powered by Disqus

Copyright © 2018 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.