Fontaine Sarah N, Martin Mackenzie D, Dickey Chad A
Department of Molecular, 4001 E Fletcher Ave MDC 36, Tampa, FL, 33613, USA.
Curr Top Med Chem. 2016;16(25):2741-52. doi: 10.2174/1568026616666160413140741.
The growing prevalence of individuals diagnosed with neurodegenerative disorders has brought into sharp relief the lack of treatment options for individuals struggling with these diseases. As more is discovered about the mechanisms of these neurodegenerative conditions, increasing evidence indicates a common theme in these proteinopathies is altered cellular protein homeostasis. In particular, the interactions of disease-associated proteins with the major cellular chaperones, heat shock proteins90 kDa and 70 kDa (Hsp90/Hsp70), are changed. Therefore, a promising strategy for therapeutic intervention is chemical inhibition and modification of these molecular chaperone proteins. Here we review the rationale behind therapeutic strategies targeting Hsp70 and its complement of co-chaperones, and describe the current literature regarding the use of small molecule inhibitors of Hsp70 in models of neurodegenerative disease.
被诊断患有神经退行性疾病的个体越来越多，这凸显了这些疾病患者缺乏治疗选择的问题。随着对这些神经退行性疾病机制的了解越来越多，越来越多的证据表明，这些蛋白质病的一个共同主题是细胞蛋白质稳态的改变。特别是，疾病相关蛋白与主要细胞伴侣蛋白90 kDa和70 kDa热休克蛋白（Hsp90/Hsp70）的相互作用发生了变化。因此，一种有前景的治疗干预策略是对这些分子伴侣蛋白进行化学抑制和修饰。在这里，我们回顾了针对Hsp70及其共伴侣蛋白的治疗策略背后的基本原理，并描述了目前关于在神经退行性疾病模型中使用Hsp70小分子抑制剂的文献。
