脱乌比基化酶 乌比基特异蛋白酶 7 和 10 调节 TAU 聚合
Christiane Volbracht1, Karina Fog1
1Neuroscience, H. Lundbeck A/S, 2500 Valby, Denmark.
International journal of molecular sciences
|November 27, 2025
概括
在阿尔茨海默氏病模型中,准泛素特异性蛋白酶7 (Usp7) 和10 (Usp10) 减少了病理性TAU聚合. 抑制USP7和USP10可能为病症提供一种新的治疗策略.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 微管相关蛋白TAU聚合是包括阿尔茨海默病 (AD) 在内的多种多样性疾病的标志.
- 蛋白质降解障碍和改变的无化与病理性TAU积累有关.
- 脱化酶 (DUB) 在调节蛋白质稳定性和降解途径方面发挥着至关重要的作用.
研究的目的:
- 调查DUBs在病态TAU聚合中的作用.
- 为了确定特定的DUBs调节TAU积累在tauopathies.
- 探索减少病理性TAU的潜在治疗点.
主要方法:
- 在rTg4510皮质培养中对93只小鼠DUB进行siRNA敲击屏幕.
- 利用了已识别的DUBs (Usp7和Usp10) 的药理抑制.
- 在各种神经元模型中评估TAU聚合和无处不在水平,包括皮质培养,海马片培养和被AD衍生的TAU播种的野生型神经元.
主要成果:
- 降解和抑制泛素特异性蛋白酶7 (Usp7) 和10 (Usp10) 显著降低了种子TAU聚合.
- 溶性TAU水平不受USP7和USP10抑制的影响.
- 抑制USP7和USP10增加了残留TAU含有物的多比基化.
结论:
- Usp7和Usp10通过影响依赖于无素的降解途径,有助于病态TAU的积累.
- 准USP7和USP10为阿尔茨海默氏症和相关病症提供了潜在的新疗法策略.
- 调节DUB活动为开发特征为蛋白质聚合的神经退行性疾病的治疗提供了有前途的途径.
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