title: Cholinergic System and Post-translational Modifications: An Insight on the Role in Alzheimer's Disease.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.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.
authors.forename: Touqeer
authors.initials: T
authors.lastname: Ahmed
authors.forename: Saadia
authors.initials: S
authors.lastname: Zahid
authors.forename: Aamra
authors.initials: A
authors.lastname: Mahboob
authors.forename: Syeda Mehpara
authors.initials: SM
authors.lastname: Farhat
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D006801:Humans; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D011950:Receptors, Cholinergic / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*
chemical_list: D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D000109:Acetylcholine
keywords: Acetylcholine; Alzheimer's disease; muscarinic receptors; nicotinic receptors; post translational modifications