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Review Article

亨廷顿病的转录失调：在发病机制和药理学靶向效力中的作用

卷 28, 期 14, 2021

发表于: 05 July, 2020

页: [2783 - 2806] 页: 24

弟呕挨: 10.2174/0929867327666200705225821

open access plus

摘要

亨廷顿病 (HD) 是一种遗传性神经退行性疾病，由编码关键细胞调节蛋白亨廷顿蛋白 (Htt) 的基因突变引起。胞嘧啶-腺嘌呤-鸟嘌呤 (CAG) 三核苷酸重复序列的扩增会导致功能蛋白的不当折叠，并且是大脑病理变化的初始触发因素。最近的研究表明，许多转录因子的功能失调是伴随 HD 的神经退行性过程的基础。这些干扰不仅是由野生型 Htt (WT Htt) 功能的丧失引起的，而且是由突变型 Htt (mHtt) 的作用引起的异常的发生引起的。在这篇综述中，我们旨在描述目前被认为与 HD 发病机制密切相关的转录因子的作用，即 RE1 沉默转录因子，也称为神经元限制性沉默因子 (REST/NRSF)、叉头盒蛋白(FOXPs)、过氧化物酶体增殖物激活受体 γ 共激活因子-1a (PGC1α)、热休克转录因子 1 (HSF1) 和活化 B 细胞的核因子κ轻链增强子 (NF-κB)。我们还考虑了这些因素在 HD 表型中的作用以及针对分析蛋白质的潜在药理学干预。此外，我们考虑了导致转录因子功能变化的分子操作是否可能具有治疗 HD 的临床效力。

关键词: 亨廷顿病、转录因子、转录失调、REST/NRSF、FOXPs、PGC1α、HSF1、NF-κB。

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