Cholinergic System and Post-translational Modifications: An Insight on the Role in Alzheimer's Disease

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,Pakistan

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.

Cite this article as:

Ahmed Touqeer*, Zahid Saadia, Mahboob Aamra and Farhat Mehpara Syeda, Cholinergic System and Post-translational Modifications: An Insight on the Role in Alzheimer's Disease, Current Neuropharmacology 2017; 15 (4) . https://dx.doi.org/10.2174/1570159X14666160325121145

DOI https://dx.doi.org/10.2174/1570159X14666160325121145	Print ISSN 1570-159X
Publisher Name Bentham Science Publisher	Online ISSN 1875-6190