调节TRADD以恢复细胞平衡并抑制细胞亡
Daichao Xu1,2, Heng Zhao1, Minzhi Jin1
1Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
Nature
|September 24, 2020
概括
研究人员认为TRADD是细胞死亡和平衡的关键调节剂. 通过像Apt-1这样的小分子抑制TRADD可以恢复细胞平衡,并防止疾病模型中的细胞死亡.
科学领域:
- 分子生物学
- 细胞生物学
- 神经科学
背景情况:
- 细胞死亡是人类疾病的标志,
- 虽然细胞死亡机制已被理解,但细胞死亡抑制后恢复平衡仍不清楚.
- TRADD (与TRAF相关的NF-κB激活子域含有蛋白质) 是一种适应蛋白质,涉及到细胞信号通路.
研究的目的:
- 确定细胞平衡和细胞亡的调节者.
- 研究TRADD在维持细胞平衡和预防细胞死亡中的作用.
- 探索针对TRADD治疗效益的药理策略.
主要方法:
- 研究了TRADD在调节贝克林1与K63结合的泛化和自的作用.
- 评估TRADD缺乏对RIPK1依赖性亡和蛋白质体压力诱导的亡的影响.
- 在细胞和动物模型中利用小分子ICCB-19和Apt-1来抑制TRADD功能.
主要成果:
- 通过调节贝克林1的无化,TRADD抑制了自,从而影响了细胞死亡途径.
- 缺乏TRADD会导致亡的增加,而其抑制则会阻断亡并恢复平衡.
- 小分子ICCB-19和Apt-1与TRADD结合,抑制其功能并激活自.
- 在病的小鼠模型中,TRADD抑制恢复了蛋白质稳定并减少了细胞死亡.
结论:
- TRADD是细胞平衡和细胞亡的关键调节者.
- 通过ICCB-19或Apt-1抑制TRADD显示出细胞死亡和稳态失调的疾病的治疗潜力.
- 针对TRADD为治疗蛋白质病变和其他人类疾病提供了一个有前途的策略.
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