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对于神经退行性疾病的Keap1-Nrf2轴的小分子抑制剂的最新进展和应用

Jing Wang¹, Yu Cao², Yang Lu³

¹School of Medicine, Hangzhou City University, Hangzhou, 310015, Zhejiang Province, China; Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, China; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, Zhejiang Province, China.

European journal of medicinal chemistry

|December 3, 2023

概括

凯普1-Nrf2通路保护氧化应激,是神经退行性疾病 (NDD) 的目标. 抑制Keap1-Nrf2相互作用为NDD提供了一个有前途的治疗策略.

科学领域:

神经科学是一个神经科学.
分子生物学分子生物学
药理学药理学是指药理学的学科.

背景情况:

凯尔奇类ECH相关蛋白1 (Keap1) -核因子红色素2相关因子2 (Nrf2) 途径对于细胞防御氧化应激至关重要.
这一途径越来越被认为是神经退行性疾病 (NDD) 的治疗点.

研究的目的:

审查Nrf2在NDD病原发生中的作用.
探索Keap1抑制剂和Keap1-Nrf2蛋白蛋白相互作用 (PPI) 抑制剂在NDD治疗中的治疗潜力.

主要方法:

在NDD中调查Keap1-Nrf2通路的研究文献综述.
对现有的Nrf2激活剂和新的Keap1-Nrf2 PPI抑制策略的分析.

主要成果:

在各种NDD模型中,Nrf2激活表明神经保护作用.
直接的Keap1-Nrf2 PPI抑制剂比传统的Nrf2激活剂具有优势,例如减少目标外影响.

结论:

针对Keap1-Nrf2通路,特别是通过PPI抑制,对开发新型NDD疗法具有重大前景.
对Keap1抑制剂的进一步研究是有必要的,以推进NDD治疗策略.

关键词:

在Keap1Nrf2路径中.神经退行性疾病的神经退行性疾病在 Nrf2 激活器.这是一个PPI PPI.

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