Role of Deubiquitinases in Parkinson's Disease-Therapeutic Perspectives

卷:12

Review

关键词: TERMINAL HYDROLASE L1;    UBIQUITIN-PROTEASOME SYSTEM;    S18Y POLYMORPHIC VARIANT;    MACHADO-JOSEPH-DISEASE;    ALPHA-SYNUCLEIN FATE;    UCH-L1 GENE;    MITOCHONDRIAL DYSFUNCTION;    DEUBIQUITYLATING ENZYME;    EXPRESSION ANALYSIS;    ASSOCIATION;   

DOI  :  10.3390/cells12040651

来源: SCIE

【 摘 要 】

Parkinson's disease (PD) is a neurodegenerative disorder that has been associated with mitochondrial dysfunction, oxidative stress, and defects in mitophagy as well as oc-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 & mdash;e.g., through the PINK1/Parkin pathway & mdash;which results in engulfment by the autophagosome and degradation in lysosomes. Deu-biquitinating enzymes (DUBs) can regulate this process at several levels by deubiquitinating mito-chondrial substrates and other targets in the mitophagic pathway, such as Parkin. Moreover, DUBs can affect oc-synuclein aggregation through regulation of degradative pathways, deubiquitination of oc-synuclein itself, and/or via co-localization with oc-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.