The potential roles of deubiquitinating enzymes in brain diseases

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초록

Most proteins undergo posttranslational modification such as acetylation, methylation, phosphorylation, biotinylation, and ubiquitination to regulate various cellular processes. Ubiquitin-targeted proteins from the ubiquitin-proteasome system (UPS) are degraded by 26S proteasome, along with this, deubiquitinating enzymes (DUBs) have specific activity against the UPS through detaching of ubiquitin on ubiquitin-targeted proteins. Balancing between protein expression and degradation through interplay between the UPS and DUBs is important to maintain cell homeostasis, and abnormal expression and elongation of proteins lead to diverse diseases such as cancer, diabetes, and autoimmune response. Therefore, development of DUB inhibitors as therapeutic targets has been challenging. In addition, understanding of the roles of DUBs in neurodegeneration, specifically brain diseases, has emerged gradually. This review highlights recent studies on the molecular mechanisms for DUBs, and discusses potential therapeutic targets for DUBs in cases of brain diseases. © 2020 The Author(s)

키워드

Deubiquitinating enzyme; Neurodegenerative disease; Ubiquitin; Ubiquitination; TERMINAL HYDROLASE L1; ALPHA-SYNUCLEIN; PARKINSON-DISEASE; POSTTRANSLATIONAL MODIFICATIONS; PROTEIN HOMEOSTASIS; MOLECULAR-BASIS; AMYLOID-BETA; CELL-DEATH; UBIQUITIN; AUTOPHAGY
제목
The potential roles of deubiquitinating enzymes in brain diseases
저자
Lim, Key-Hwan; Joo, Jae-Yeol; Baek, Kwang-Hyun
DOI
10.1016/j.arr.2020.101088.
발행일
2020-08
유형
정기 학술지(Review)
저널명
Ageing Research Reviews
권
61
페이지
1 ~ 9