The ubiquitin proteasome system and schizophrenia

被引:54
作者
Luza, Sandra [1 ,2 ]
Opazo, Carlos M. [1 ,2 ]
Bousman, Chad A. [1 ,4 ,5 ,6 ,7 ,8 ]
Pantelis, Christos [1 ,2 ,3 ,4 ,9 ]
Bush, Ashley I. [2 ]
Everall, Ian P. [1 ,2 ,3 ,4 ,10 ]
机构
[1] Univ Melbourne, Melbourne Neuropsychiat Ctr, Dept Psychiat, Parkville, Vic, Australia
[2] Univ Melbourne, Melbourne Dementia Res Ctr, Florey Inst Neurosci & Mental Hlth, Parkville, Vic 3052, Australia
[3] Univ Melbourne, Ctr Neural Engn, Dept Elect & Elect Engn, Parkville, Vic, Australia
[4] Cooperat Res Ctr Mental Hlth, Carlton, Vic, Australia
[5] Univ Calgary, Cumming Sch Med, Hotchkiss Brain Inst, Calgary, AB, Canada
[6] Univ Calgary, Dept Med Genet, Calgary, AB, Canada
[7] Univ Calgary, Dept Psychiat, Calgary, AB, Canada
[8] Univ Calgary, Dept Physiol & Pharmacol, Calgary, AB, Canada
[9] Northwestern Mental Hlth, Melbourne, Vic, Australia
[10] Kings Coll London, Inst Psychiat Psychol & Neurosci, London, England
来源
LANCET PSYCHIATRY | 2020年 / 7卷 / 06期
基金
澳大利亚国家健康与医学研究理事会; 英国医学研究理事会;
关键词
GENE-EXPRESSION; PREFRONTAL CORTEX; PYRAMIDAL NEURONS; EPIGENETIC REGULATION; BIPOLAR DISORDER; CIRCADIAN CLOCK; ALPHA-SYNUCLEIN; PROTEIN; UCH-L1; UBE3A;
D O I
10.1016/S2215-0366(19)30520-6
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
The ubiquitin-proteasome system is a master regulator of neural development and the maintenance of brain structure and function. It influences neurogenesis, synaptogenesis, and neurotransmission by determining the localisation, interaction, and turnover of scaffolding, presynaptic, and postsynaptic proteins. Moreover, ubiquitin-proteasome system signalling transduces epigenetic changes in neurons independently of protein degradation and, as such, dysfunction of components and substrates of this system has been linked to a broad range of brain conditions. Although links between ubiquitin-proteasome system dysfunction and neurodegenerative disorders have been known for some time, only recently have similar links emerged for neurodevelopmental disorders, such as schizophrenia. Here, we review the components of the ubiquitin-proteasome system that are reported to be dysregulated in schizophrenia, and discuss specific molecular changes to these components that might, in part, explain the complex causes of this mental disorder.
引用
收藏
页码:528 / 537
页数:10
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