Proteasome-Associated Syndromes: Updates on Genetics, Clinical Manifestations, Pathogenesis, and Treatment.

Autor: Zhang J; Department of Rheumatology, The Second Affiliated Hospital, Zhejiang University School of Medicine, and Liangzhu Laboratory, Zhejiang University, Hangzhou, China.; National Clinical Research Center for Kidney Diseases, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China., Tao P; Department of Rheumatology, The Second Affiliated Hospital, Zhejiang University School of Medicine, and Liangzhu Laboratory, Zhejiang University, Hangzhou, China. taopanfeng@zju.edu.cn., Deuitch NT; Inflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA., Yu X; Department of Rheumatology, The Second Affiliated Hospital, Zhejiang University School of Medicine, and Liangzhu Laboratory, Zhejiang University, Hangzhou, China. yuxiaomin78@gmail.com., Askentijevich I; Inflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA., Zhou Q; Department of Rheumatology, The Second Affiliated Hospital, Zhejiang University School of Medicine, and Liangzhu Laboratory, Zhejiang University, Hangzhou, China. zhouqingnwu@gmail.com.
Jazyk: angličtina
Zdroj: Journal of clinical immunology [J Clin Immunol] 2024 Apr 05; Vol. 44 (4), pp. 88. Date of Electronic Publication: 2024 Apr 05.
DOI: 10.1007/s10875-024-01692-y
Abstrakt: The ubiquitin-proteasome system (UPS) has a critical role in post-translational protein modification that is essential for the maintenance of all cellular functions, including immune responses. The proteasome complex is ubiquitously expressed and is responsible for degradation of short-lived structurally abnormal, misfolded and not-needed proteins that are targeted for degradation via ubiquitin conjugation. Over the last 14 years, an increasing number of human diseases have been linked to pathogenic variants in proteasome subunits and UPS regulators. Defects of the proteasome complex or its chaperons - which have a regulatory role in the assembly of the proteasome - disrupt protein clearance and cellular homeostasis, leading to immune dysregulation, severe inflammation, and neurodevelopmental disorders in humans. Proteasome-associated diseases have complex inheritance, including monogenic, digenic and oligogenic disorders and can be dominantly or recessively inherited. In this review, we summarize the current known genetic causes of proteasomal disease, and discuss the molecular pathogenesis of these conditions based on the function and cellular expression of mutated proteins in the proteasome complex.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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