Carboxy-terminus of Hsc70-interacting protein (CHIP) functions both as a molecular co-chaperone and ubiquitin E3 ligase playing a critical role in modulating the degradation of numerous chaperone-bound proteins. To date, it has been implicated in the regulation of numerous biological functions, including misfolded-protein refolding, autophagy, immunity, and necroptosis. Moreover, the ubiquitous expression of CHIP in the central nervous system suggests that it may be implicated in a wide range of functions in neurological diseases. Several recent studies of our laboratory and other groups have highlighted the beneficial role of CHIP in the pathogenesis of several neurological diseases. The objective of this review is to discuss the possible molecular mechanisms that contribute to the pathogenesis of neurological diseases in which CHIP has a pivotal role, such as stroke, intracerebral hemorrhage, Alzheimer’s disease, Parkinson’s disease, and polyglutamine diseases; furthermore, CHIP mutations could also cause neurodegenerative diseases. Based on the available literature, CHIP overexpression could serve as a promising therapeutic target for several neurological diseases.

Hsc70 相互作用蛋白 (CHIP) 的羧基末端既是分子共伴侣，又是泛素 E3 连接酶，在调节众多伴侣结合蛋白的降解中起关键作用。迄今为止，它参与了许多生物功能的调节，包括错误折叠的蛋白质重折叠、自噬、免疫和坏死性凋亡。此外，CHIP 在中枢神经系统中的普遍表达表明它可能与神经系统疾病的广泛功能有关。我们实验室和其他小组最近的几项研究强调了 CHIP 在几种神经系统疾病发病机制中的有益作用。本综述的目的是讨论导致 CHIP 发挥关键作用的神经系统疾病发病机制的可能分子机制，如中风、脑出血、阿尔茨海默病、帕金森病和多聚谷氨酰胺疾病；此外，CHIP 突变也可能导致神经退行性疾病。根据现有文献，CHIP 过表达可以作为几种神经系统疾病的有希望的治疗靶点。