Luza Sandra, Opazo Carlos M, Bousman Chad A, Pantelis Christos, Bush Ashley I, Everall Ian P
Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne & Melbourne Health, Parkville, VIC, Australia; Melbourne Dementia Research Centre, Florey Institute of Neuroscience and Mental Health, The University of Melbourne & Melbourne Health, Parkville, VIC, Australia.
Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne & Melbourne Health, Parkville, VIC, Australia; The Cooperative Research Centre for Mental Health, Carlton South, VIC, Australia; Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Departments of Medical Genetics, Psychiatry, and Physiology & Pharmacology, University of Calgary, Calgary, AB, Canada; University of Calgary, Calgary, AB, Canada.
Lancet Psychiatry. 2020 Jun;7(6):528-537. doi: 10.1016/S2215-0366(19)30520-6. Epub 2020 Feb 12.
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.
泛素-蛋白酶体系统是神经发育以及脑结构和功能维持的主要调节因子。它通过决定支架蛋白、突触前蛋白和突触后蛋白的定位、相互作用及周转，影响神经发生、突触形成和神经传递。此外，泛素-蛋白酶体系统信号传导可独立于蛋白质降解介导神经元的表观遗传变化，因此，该系统的组分和底物功能障碍与多种脑部疾病有关。虽然泛素-蛋白酶体系统功能障碍与神经退行性疾病之间的联系已为人所知一段时间，但直到最近，类似的联系才在诸如精神分裂症等神经发育障碍中出现。在此，我们综述了据报道在精神分裂症中失调的泛素-蛋白酶体系统的组分，并讨论这些组分的特定分子变化，这些变化可能部分解释了这种精神障碍的复杂病因。
