SCIRP Mobile Website
Paper Submission

Why Us? >>

  • - Open Access
  • - Peer-reviewed
  • - Rapid publication
  • - Lifetime hosting
  • - Free indexing service
  • - Free promotion service
  • - More citations
  • - Search engine friendly

Free SCIRP Newsletters>>

Add your e-mail address to receive free newsletters from SCIRP.


Contact Us >>

Article citations


Liskowsky, W. and Schliebs, R. (2006) Muscarinic acetylcholine receptor inhibition in transgenic Alzheimer-like Tg2576 mice by scopolamine favours the amyloidogenic route of processing of amyloid precursor protein. International Journal of Developmental Neuroscience, 24, 149-156.

has been cited by the following article:

  • TITLE: Accelerating Alzheimer’s pathogenesis by GRK5 deficiency via cholinergic dysfunction

    AUTHORS: William Z. Suo

    KEYWORDS: G Protein; Receptor; Kinase; Cholinergic; Alzheimer; Pathogenesis

    JOURNAL NAME: Advances in Alzheimer's Disease, Vol.2 No.4, December 3, 2013

    ABSTRACT: G protein-coupled receptors (GPCRs) mediate a wide variety of physiological function. GPCR signaling is negatively regulated by the receptor desensitization, a procedure initiated by a group of kinases, including GPCR kinases (GRKs). Studies using genetargeted mice revealed that deficiency of a particular GRK member led to dysfunction of a highly selective group of GPCRs. In particular, for example, GRK5 deficiency specifically disrupts M2/M4-mediated muscarinic cholinergic function. Emerging evidence indicates that ?-amyloid accumulation may lead to GRK5 deficiency, while the latter impairs desensitization of M2/M4 receptors. Within memory circuits, M2 is primarily presynaptic autoreceptor serving as a negative feedback to inhibit acetylcholine release. The impaired desensitization of M2 receptor by GRK5 deficiency leads to hyperactive M2, which eventually suppresses acetylcholine release and results in an overall cholinergic hypofunctioning. Since the cholinergic hypofunctioning is known to cause ?-amyloid accumulation, the GRK5 deficiency appears to connect the cholinergic hypofunctioning and ?-amyloid accumulation together into a self-amplifying cycle, which accelerates both changes. Given that the ? -amyloid accumulation and the cholinergic hypofucntioning are the hallmark changes in the ?-amyloid hypothesis and the cholinergic hypothesis, respectively, the GRK5 deficiency appears to bring the two major hypotheses in Alzheimer’s disease together, whereas the GRK5 deficiency is the pivotal link. Therefore, any strategies that can break this cycle would be therapeutically beneficial for Alzheimer’s patients.