Title: G Protein-Coupled Receptors, Cholinergic Dysfunction, and A beta Toxicity in Alzheimer's Disease
Authors: Thathiah, Amantha
De Strooper, Bart # ×
Issue Date: Oct-2009
Publisher: American Association for the Advancement of Science
Series Title: Science Signaling vol:2 issue:93
Article number: -
Abstract: The beta-amyloid (A beta) peptide is associated with the pathogenesis of Alzheimer's disease (AD). Evidence gathered over the last two decades suggests that the gradual accumulation of soluble and insoluble A beta peptide species triggers a cascade of events that leads to the clinical manifestation of AD. A beta accumulation has also been associated with the cholinergic dysfunction observed in AD, which is characterized by diminished acetylcholine release and impaired coupling of the muscarinic acetylcholine receptors (mAChRs) to heterotrimeric GTP-binding proteins (G proteins). Although the mechanism of A beta-mediated toxicity is not clearly understood, evidence shows that A beta accumulation has an effect on the oligomerization of the angiotensin II (AngII) AT(2) (angiotensin type 2) receptor and sequestration of the G alpha(q/11) family of G proteins. Sequestration of G alpha(q/11) results in dysfunctional coupling and signaling between M-1 mAChR and G alpha(q/11) and accompanies neurodegeneration, tau phosphorylation, and neuronal loss in an AD transgenic mouse model. Collectively, these results provide a putative link among A beta toxicity, AT(2) receptor oligomerization, and disruption of the signaling pathway through M-1 mAChR and G alpha(q/11) and potentially contribute to our understanding of the cholinergic deficit observed in AD.
ISSN: 1945-0877
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Laboratory for the Research of Neurodegenerative Diseases
× corresponding author
# (joint) last author

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