Ubiquitin carboxyl-terminal hydrolase L-1 in brain: Focus on its oxidative/nitrosative modification and role in brains of subjects with Alzheimer disease and mild cognitive impairment.
Ubiquitin carboxyl-terminal hydrolase L-1 in brain: Focus on its oxidative/nitrosative modification and role in brains of subjects with Alzheimer disease and mild cognitive impairment.
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DOI：
10.1016/j.freeradbiomed.2021.10.036
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发表时间：
2021-12
影响因子：
7.4
通讯作者：
Butterfield DA
中科院分区：
文献类型：
--
作者：
Butterfield DA
神经元必须去除聚集的、受损的蛋白质才能生存。促进这种蛋白质质量控制的方法之一是泛素-蛋白酶体系统（UPS）。聚集的、受损的蛋白质通过获得泛素残基的聚合物作为转运到UPS的信号而被UPS靶向破坏。然而，在这种蛋白质降解发生之前，必须去除多聚泛素链，一次一个残基，这是由泛素C末端水解酶（UCH-L1）促进的反应。在阿尔茨海默病大脑中，这种通常丰富的蛋白质与对照大脑相比水平较低，并且经过氧化和亚硝化修饰。这导致多效性UCH-L1酶的功能减弱，从而导致AD脑中的病理改变，作者断言UCH-L1的氧化和亚硝化改变是这种毁灭性痴呆症及其早期阶段轻度认知障碍（MCI）中神经元死亡机制的主要贡献者。本文综述了AD和MCI脑中的这些发现。
Neurons must remove aggregated, damaged proteins in order to survive. Among the ways of facilitating this protein quality control is the ubiquitin-proteasomal system (UPS). Aggregated, damaged proteins are targeted for destruction by the UPS by acquiring a polymer of ubiquitin residues that serves as a signal for transport to the UPS. However, before this protein degradation can occur, the polyubiquitin chain must be removed, one residue at a time, a reaction facilitated by the enzyme, ubiquitin C-terminal hydrolase (UCH-L1). In Alzheimer disease brain, this normally abundant protein is both of lower levels and oxidatively and nitrosatively modified than in control brain. This causes diminished function of the pleiotropic UCH-L1 enzyme with consequent pathological alterations in AD brain, and the author asserts the oxidative and nitrosative alterations of UCH-L1 are major contributors to mechanisms of neuronal death in this devastating dementing disorder and its earlier stage, mild cognitive impairment (MCI). This review paper outlines these findings in AD and MCI brain.
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影响因子：
16.6
作者：
Ashton NJ;Janelidze S;Al Khleifat A;Leuzy A;van der Ende EL;Karikari TK;Benedet AL;Pascoal TA;Lleó A;Parnetti L;Galimberti D;Bonanni L;Pilotto A;Padovani A;Lycke J;Novakova L;Axelsson M;Velayudhan L;Rabinovici GD;Miller B;Pariante C;Nikkheslat N;Resnick SM;Thambisetty M;Schöll M;Fernández-Eulate G;Gil-Bea FJ;López de Munain A;Al-Chalabi A;Rosa-Neto P;Strydom A;Svenningsson P;Stomrud E;Santillo A;Aarsland D;van Swieten JC;Palmqvist S;Zetterberg H;Blennow K;Hye A;Hansson O
通讯作者：
Hansson O
DOI：
10.1042/bcj20160082
发表时间：
2016-08-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Bishop P;Rocca D;Henley JM
通讯作者：
Henley JM
影响因子：
4.8
作者：
Choi, J;Levey, AI;Li, L
通讯作者：
Li, L
影响因子：
4.7
作者：
Butterfield DA;Boyd-Kimball D
通讯作者：
Boyd-Kimball D
影响因子：
7.4
作者：
Castegna, A;Aksenov, M;Butterfield, DA
通讯作者：
Butterfield, DA