Deciphering the Role of Aberrant Protein Post-Translational Modification in the Pathology of Neurodegeneration

Title:Deciphering the Role of Aberrant Protein Post-Translational Modification in the Pathology of Neurodegeneration

Volume: 20 Issue: 1

Author(s): Sadat Shafi, Archu Singh, Paras Gupta, Pooja A. Chawla, Faizana Fayaz, Anjali Sharma and Faheem H. Pottoo*

Affiliation:

• Department of Pharmacology, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam 31441,Saudi Arabia

Keywords: Neurodegenerative diseases, post-translational modification, neuronal dysfunction, phosphorylation, acetylation, palmitoylation, SUMOylation, ubiquitination.

Abstract: Neurodegenerative diseases, including Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Amyotrophic Lateral Sclerosis (ALS) and Huntington's Disease (HD), are characterized by progressive neuronal dysfunction and death. Recent studies have established detrimental modifications in the structure and function of brain proteins, which stimulate their aggregation, misfolding and deposition in and around the neurons an important hallmark of neurodegenerative diseases. Post-Translational Modification (PTM) of proteins, including phosphorylation, acetylation, glycosylation, palmitoylation, SUMOylation, and ubiquitination, are important regulators of protein characteristics, including stability, intracellular distribution, activity, interactions, aggregation and clearance. Despite clear evidence that altered protein modifications emerging from impromptu chemical modifications to side chains of amino acid are associated with neurodegeneration, the underlying mechanisms that promote aberrant PTM remain poorly understood. Therefore, elucidating PTM of specific disease-associated proteins can prove to be a significant step in evaluating the functional alteration of proteins and their association with neurodegeneration. This review describes how aberrant PTM of various proteins is linked with the neurodegenerative disease pathogenesis, as well as molecular strategies targeting these modifications for treating such diseases, which are yet incurable.

Cite this article as:

Shafi Sadat , Singh Archu , Gupta Paras , Chawla A. Pooja , Fayaz Faizana, Sharma Anjali and Pottoo H. Faheem*, Deciphering the Role of Aberrant Protein Post-Translational Modification in the Pathology of Neurodegeneration, CNS & Neurological Disorders - Drug Targets 2021; 20 (1) . https://dx.doi.org/10.2174/1871527319666200903162200