Title:Cholinergic System and Post-translational Modifications: An Insight on the Role in Alzheimer's Disease
VOLUME: 15 ISSUE: 4
Author(s):Touqeer Ahmed*, Saadia Zahid, Aamra Mahboob and Syeda Mehpara Farhat
Affiliation:Neurobiology Laboratory, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology P.O. Box: 44000, Sector H-12, Islamabad
Keywords:Acetylcholine, Alzheimer's disease, muscarinic receptors, nicotinic receptors, post translational modifications.
Abstract:Background: Alzheimer’s disease (AD) is the most common form of old age dementia.
The formation of amyloid plaques (Aβ), neurofibrillary tangles and loss of basal forebrain
cholinergic neurons are the hallmark events in the pathology of AD.
Literature Review: Cholinergic system is one of the most important neurotransmitter system
involved in learning and memory which preferentially degenerates in the initial stages of AD.
Activation of cholinergic receptors (muscarinic and nicotinic) activates multiple pathways which
result in post translational modifications (PTMs) in multiple proteins which bring changes in nervous
system. Cholinergic receptors-mediated PTMs “in-part” substantially affect the biosynthesis, proteolysis,
degradation and expression of many proteins and in particular, amyloid precursor protein (APP). APP is
subjected to several PTMs (proteolytic processing, glycosylation, sulfation, and phosphorylation)
during its course of processing, resulting in Aβ deposition, leading to AD. Aβ also alters the PTMs
of tau which is a microtubule associated protein. Therefore, post-translationally modified tau and Aβ
collectively aggravate the neuronal loss that leads to cholinergic hypofunction.
Conclusion: Despite the accumulating evidences, the interaction between cholinergic neurotransmission
and the physiological significance of PTM events remain speculative and still needs
further exploration. This review focuses on the role of cholinergic system and discusses the significance
of PTMs in pathological progression of AD and highlights some important future directions.
