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Role of Deubiquitinases in Parkinson's Disease-Therapeutic Perspectives.
| Content Provider | Europe PMC |
|---|---|
| Author | Nielsen, Pernille Y. Ø. Okarmus, Justyna Meyer, Morten |
| Editor | Gaillard, Afsaneh |
| Copyright Year | 2023 |
| Abstract | Parkinson’s disease (PD) is a neurodegenerative disorder that has been associated with mitochondrial dysfunction, oxidative stress, and defects in mitophagy as well as α-synuclein-positive inclusions, termed Lewy bodies (LBs), which are a common pathological hallmark in PD. Mitophagy is a process that maintains cellular health by eliminating dysfunctional mitochondria, and it is triggered by ubiquitination of mitochondrial-associated proteins—e.g., through the PINK1/Parkin pathway—which results in engulfment by the autophagosome and degradation in lysosomes. Deubiquitinating enzymes (DUBs) can regulate this process at several levels by deubiquitinating mitochondrial substrates and other targets in the mitophagic pathway, such as Parkin. Moreover, DUBs can affect α-synuclein aggregation through regulation of degradative pathways, deubiquitination of α-synuclein itself, and/or via co-localization with α-synuclein in inclusions. DUBs with a known association to PD are described in this paper, along with their function. Of interest, DUBs could be useful as novel therapeutic targets against PD through regulation of PD-associated defects. |
| Journal | Cells |
| Volume Number | 12 |
| PubMed Central reference number | PMC9954239 |
| Issue Number | 4 |
| PubMed reference number | 36831318 |
| e-ISSN | 20734409 |
| DOI | 10.3390/cells12040651 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2023-02-17 |
| Access Restriction | Open |
| Rights License | Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). © 2023 by the authors. |
| Subject Keyword | neurodegeneration PARK2 parkin mitochondria protein degradation ubiquitin proteasome system mitophagy α-synuclein Lewy bodies |
| Content Type | Text |
| Resource Type | Article |
| Subject | Biochemistry, Genetics and Molecular Biology |
