Cholinergic muscarinic receptor signaling by the phosphoinositide signal transduction system in Alzheimer's disease

摘要: Recent years have seen the advent of new methods capable measuring activity receptor-coupled, G-protein-mediated, phosphoinositide second messenger production in membranes prepared from postmortem human brain. Considering interest treating Alzheimer's disease (AD) patients with cholinergic agonists, several investigations used this methodology to analyze functional state muscarinic receptors coupled signaling directly AD Several, but not all, reports indicate that agonist-induced is severely impaired AD, potentially due activation receptor-coupled G-protein. Additionally, deficits also been reported two pathways activated following hydrolysis, inositol-1,4,5,-triphosphate receptor binding and protein kinase C activation, indicating further AD. Sources limitations current methodologies issues for exploration are discussed. Speculation concerning potential links between receptor-linked early events formation amyloid plaques neurofibrillary tangles provided. Especially intriguing development synergistic neurotoxicity where increased A beta interact exacerbate alterations each process occur leading a feed-forward cycle progressive neuronal dysfunction.