Cellular functions regulated by deubiquitinating enzymes in neurodegenerative diseases

Ageing Res Rev. 2021 May 20:101367. doi: 10.1016/j.arr.2021.101367. Online ahead of print.ABSTRACTNeurodegenerative diseases are one of the most common diseases in mankind. Although there are reports of several candidates that cause neurodegenerative diseases, the exact mechanism of pathogenesis is poorly understood. The ubiquitin-proteasome system (UPS) is an important posttranslational modification for protein degradation and control of homeostasis. Enzymes such as E1, E2, E3 ligases, and deubiquitinating enzymes (DUBs) participating in UPS, regulate disease-inducing proteins by controlling the degree of ubiquitination. Therefore, the development of treatments targeting enzymes for degenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), is emerging as an attractive perspective. In particular, as DUBs are able to regulate one or more degenerative disease-related proteins, the potential as a therapeutic target is even more evident. DUBs influence the regulation of toxic proteins that cause neurodegenerative diseases by not only their removal, but also by regulating signals associated with mitophagy, autophagy, and endoplasmic reticulum-associated degradation (ERAD). In this review, we analyze not only the cellular processes of DUBs, which control neurodegenerative disease-inducing proteins, but also their potentials as a therapeutic agent for neurodegenerative diseases.PMID:34023421 ...
Source: Ageing Research Reviews - Category: Genetics & Stem Cells Authors: Source Type: research