肌肉生理学和疾病中的deubiquitinases
Cyriel S Olie1, Darragh P O'Brien2, Hannah B L Jones2
1Department of Human Genetics, Leiden University Medical Centre, 2333ZC Leiden, The Netherlands.
Biochemical Society transactions
|May 8, 2024
概括
脱化酶 (DUBs) 通过调节蛋白质平衡,对肌肉健康和功能至关重要. 准DUB为肌肉疾病和与年龄有关的肌肉损失提供了潜在的新疗法.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 神经科学是一个神经科学.
背景情况:
- 肌肉和神经元细胞的功能依赖于蛋白质稳定,其中泛素-蛋白质酶系统 (UPS) 是一个关键的调节器.
- UPS功能障碍与肌肉衰老和神经肌肉疾病 (NMD) 有关,导致蛋白质积累和功能缺陷.
- 脱化酶 (DUB) 是UPS的重要组成部分,控制蛋白质的循环和泛素水平.
研究的目的:
- 审查DUBs在肌肉生理学和NMDs中的参与.
- 突出DUBs在肌肉再生,退化和炎症中的作用.
- 探索针对肌肉疾病的DUB的治疗潜力.
主要方法:
- 文献综述侧重于DUBs,蛋白质稳定,肌肉衰老和神经肌肉疾病.
- 对DUB突变与人类NMDs之间的遗传联系的分析.
- 检查DUB参与肌肉再生,退化和神经肌肉结合功能.
主要成果:
- 在DUB基因 (例如,ATXN3,USP14) 中的突变与人类的NMDs有关.
- 像USP5,USP9X和USP14这样的DUB对神经肌肉结合功能至关重要.
- DUB失调影响肌肉再生,退化和炎症.
- 在小鼠中,USP19缺乏促进肌肉质量维护.
结论:
- DUBs对于维持肌肉健康至关重要,并与衰老和NMDs有关.
- 功能障碍的DUBs有助于异常的蛋白质积累和肌肉病理.
- 针对DUBs为各种肌肉疾病提供了一个有前途的治疗策略,包括肉症和缓冲症.
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