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Mitochondrial Dysfunction and Alzheimer’s Disease

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DOI: 10.4236/ojemd.2013.32A003    4,668 Downloads   8,566 Views   Citations

ABSTRACT

Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by progressive loss of basal forebrain cholinergic neurons, leading to reduction in transmission through cholinergic fibers involved in processes of attention, learning, and memory. Mitochondria provide and regulate cellular energy and are crucial for proper neuronal activity and survival. Mitochondrial dysfunction is evident in early stages of AD and is involved in AD pathogenesis. This review focuses on the evidence supporting a clear association between amyloid-β toxicity, mitochondrial dysfunction, oxidative stress and neuronal damage/death in Alzheimer’s disease. To date, the beta amyloid (Aβ) cascade hypothesis still remains the main pathogenetic model of Alzheimer’s disease (AD), but its role in the majority of sporadic AD cases is uncertain. Furthermore, the “mitochondrial cascade hypothesis” could explain many of the biochemical, genetic, and pathological features of sporadic AD. This hypothesis promotes mutations in mitochondrial DNA (mtDNA) as the basis for Alzheimer’s disease. The mutations could lead to energy failure, increased oxidative stress, and accumulation of Aβ, which in a vicious cycle reinforces the mtDNA damage and oxidative stress.

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F. Albrekkan and M. Kelly-Worden, "Mitochondrial Dysfunction and Alzheimer’s Disease," Open Journal of Endocrine and Metabolic Diseases, Vol. 3 No. 2A, 2013, pp. 14-19. doi: 10.4236/ojemd.2013.32A003.

References

[1] C. Lee, P. Linneman and M. J. Berridge, “Calcium Hypothesis of Alzheimer’s Disease,” European Journal of Physiology, Vol. 459, No. 3, 2010, pp. 441-449. doi:10.1007/s00424-009-0736-1
[2] C. Supnet and I. Bezprozvanny, “Presenilins as Endoplasmic Reticulum Calcium Leak Channels and Alzheimer’s Disease Pathogenesis,” Science China Life Sciences, Vol. 54, No. 8, 2011, pp. 744-751. doi:10.1007/s11427-011-4201-y
[3] J. Pitt, W. Roth, P. Lacor, A. B. Smith III, M. Blankenship, P. Velasco, F. D. Felice, P. Breslin and W. L. Klein, “Alzheimer’s-Associated Aβ Oligomers Show Altered Structure, Immunoreactivity and Synaptotoxicity with Low Doses of Oleocanthal,” Toxicology and Applied Pharmacology, Vol. 240, No. 2, 2009, pp. 189-197. doi:10.1016/j.taap.2009.07.018
[4] M. Mancuso, G. Siciliano, M. Filosto and L. Murri, “Mitochondrial Dysfunction and Alzheimer’s Disease: New Developments,” Journal Of Alzheimer’s Disease, Vol. 9, No. 2, 2006, pp. 111-117.
[5] R. D. Readnower, A. D. Sauerbeck and B. G. Sullivan, “Mitochondria, Amylpoid B, and Alzheimer’s Disease,” International Journal of Alzheimer Disease, Vol. 2011, Article ID: 104545, 2011, pp. 1-5. doi:10.4061/2011/104545
[6] P. I. Moreira, S. M. Cardoso, M. S. Santos and C. R. Oliveira, “The Key Role of Mitochondria in Alzheimer’s Disease,” Journal of Alzheimer’s Disease, Vol. 9, No. 2, 2006, pp. 101-110.
[7] I. Onyango, S. Khan, B. Miller, R. Swerdlow, P. Trimmer and J. Bennett Jr., “Mitochondrial Genomic Contribution to Mitochondrial Dysfunction in Alzheimer’s Disease,” Journal of Alzheimer’s Disease, Vol. 9, No. 2, 2006, pp. 183-193.
[8] P. A. Trimmer and M. K. Borland, “Differentiated Alzheimer’s Disease Transmitochondrial Cybrid Cell Lines Exhibit Reduced Organelle Movements,” Antioxid Redox Signaling, Vol. 7, No. 9-10, 2005, pp. 1101-1109. doi:10.1089/ars.2005.7.1101
[9] E. Area-Gomez, J. C. de Groof, I. Boldogh, T. D. Bird, G. E. Gibson, C. M. Koehler, W. H. Yu, K. E. Duff, M. P. Yaffe, L. A. Pon and E. A. Schon, “Presenilins Are Enriched in Endoplasmic Reticulum Membranes Associated with Mitochondria,” The American Journal of Pathology, Vol. 175, No. 5, 2009, pp. 1810-1816. doi:10.2353/ajpath.2009.090219
[10] M. Dumont, M. T. Lin and M. F. Beal, “Mitochondria and Antioxidant Targeted Therapeutic Strategies for Alzheimer’s Disease,” Journal of Alzheimer’s Disease, Vol. 20, 2010, pp. 633-643.
[11] J. Zhang, J. Asin-Cayuela, J. Fish, Y. Michikawa, M. Bonafé, F. Olivieri, G. Passarino, G. De Benedictis, C. Franceschi and G. Attardi, “Strikingly Higher Frequency in Centenarians and Twins of mtDNA Mutation Causing Remodeling of Replication Origin in Leukocytes,” Proceedings of National Academy of Science of USA, Vol. 100, No. 3, 2003, pp. 1116-1121. doi:10.1073/pnas.242719399
[12] A. Eckert, K. L. Schulz, V. Rhein and J. Gotz, “Convergence of Amyloid-βand Tau Pathologies on Mitochondria in Vivo,” Molecular Neurobiology, Vol. 41, No. 2-3, 2010, pp. 107-114. doi:10.1007/s12035-010-8109-5
[13] R. Castellani, K. Hirai, G. Aliev, K. Drew, A. Nunomura, A. Takeda, A. D. Cash, M. E. Obrenovich, G. Perry and M. A. Smith, “Role of Mitochondrial Dysfunction in Alzheimer’s Disease,” Journal of Neuroscience Research, Vol. 70, No. 3, 2002, pp. 357-360. doi:10.1002/jnr.10389
[14] A. K. Niemi, J. S. Moilanen, M. Tanaka, A. Hervonen, M. Hurme, T. Lehtimaki, Y. Arai, N. Hirose and K. Majamaa. “A Combination of Three Common Inherited Mitochondrial DNA Polymorphisms Promotes Longevity in Finnish and Japanese Subject,” European Journal of Human Genetics, Vol. 13, 2005, pp. 166-170. doi:10.1038/sj.ejhg.5201308
[15] S. D. Yan and D. M. Stern, “Mitochondrial Dysfunction and Alzheimer’s Disease: Role of Amyloid-β Peptide Alcohol Dehydrogenase (ABAD),” International Journal of Experimental Pathology, Vol. 86, No. 3, 2005, pp. 161-171. doi:10.1111/j.0959-9673.2005.00427.x
[16] He X.Y., MerZ G., Mehta P., SchulZ H., Yang S.Y. “Human Brain Short Chain L-3-hydroxyacyl-coenzyme A Dehydrogenase Is a Single-Domain Multifunctional Enzyme: Characterization of a Novel 17β-Hydroxysteroid Dehydrogenase,” Journal of Biological Chemistry, Vol. 274, 1999, pp. 15014-15019. doi:10.1074/jbc.274.21.15014
[17] E. A. Schon and E. Area-Gomez, “Is Alzheimer’s Disease a Disorder of Mitochondria-Associated Membranes?” Journal of Alzheimer’s Disease, Vol. 20, No. 2, 2010, pp. S281-S292.
[18] V. A. Morais and B. D. Strooper, “Mitochondria Dysfunction and Neurodegenerative Disorders: Cause or Consequence,” Journal of Alzheimer’s Disease, Vol. 20, No. 4, 2010, pp. 255-263.
[19] J. E.Vance, “Molecular and Cell Biology of Phosphatidylserine and Phosphatidylethanolamine Metabolism,” Progress in Nucleic Acid Research and Molecular Biology, Vol. 75, 2003, pp. 69-111. doi:10.1016/S0079-6603(03)75003-X
[20] M. Mancuso, V. Calsolaro, D. Orsucci, C. Carlesi, A. Choub, S. Piazza and G. Siciliano, “Mitochondria, Cognitive Impairment, and Alzheimer’s Disease,” International Journal of Alzheimer’s Disease, Vol. 2009, Article ID: 951548, 2009, pp. 1-8. doi:10.4061/2009/951548
[21] S. M. Cardoso, I. Santana, H. Russell, Swerdlow and C. R. Oliveira, “Mitochondria Dysfunction of Alzheimer’s Disease Cybrids Enhances Aβ Toxicity,” Journal of Neurochemistry, Vol. 89, No. 6, 2004, pp. 1417-1426. doi:10.1111/j.1471-4159.2004.02438.x
[22] S. M. Cardoso, M. T. Proenca, S. Santos, I. Santana and C. R. Oliveira, “Cytochrome C Oxidase is Decreased in Alzheimer’s Disease Platelets,” Neurobiology of Aging, Vol. 25, No. 1, 2004, pp. 105-110. doi:10.1016/S0197-4580(03)00033-2

  
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