Post-translational modifications: Regulators of neurodegenerative proteinopathies

Ageing Res Rev. 2021 Mar 25:101336. doi: 10.1016/j.arr.2021.101336. Online ahead of print.ABSTRACTOne of the hallmark features in the neurodegenerative disorders (NDDs) is the accumulation of aggregated and/or non-functional protein in the cellular milieu. Post-translational modifications (PTMs) are an essential regulator of non-functional protein aggregation in the pathogenesis of NDDs. Any alteration in the post-translational mechanism and the protein quality control system, for instance, molecular chaperone, ubiquitin-proteasome system, autophagy-lysosomal degradation pathway, enhances the accumulation of misfolded protein, which causes neuronal dysfunction. Post-translational modification plays many roles in protein turnover rate, accumulation of aggregate and can also help in the degradation of disease-causing toxic metabolites. PTMs such as acetylation, glycosylation, phosphorylation, ubiquitination, palmitoylation, SUMOylation, nitration, oxidation, and many others regulate protein homeostasis, which includes protein structure, functions and aggregation propensity. Different studies demonstrated the involvement of PTMs in the regulation of signaling cascades such as PI3K/Akt/GSK3β, MAPK cascade, AMPK pathway, and Wnt signaling pathway in the pathogenesis of NDDs. Further, mounting evidence suggests that targeting different PTMs with small chemical molecules, which acts as an inhibitor or activator, reverse misfolded protein accumulation and thus enhances the neuroprot...
Source: Ageing Research Reviews - Category: Genetics & Stem Cells Authors: Source Type: research