摘 要：摘 要：CHIP属于连接酶类，具有E3泛素连接酶活性，参与能量代谢途径和新陈代谢。包括阿尔茨海默病(Alzheimer{$39}s disease, AD)、帕金森病(Parkinson{$39}s disease, PD)、亨廷顿病(Huntington{$39}s disease, HD)等在内的神经退行性疾病的主要病理学特征之一——细胞中异常蛋白的聚集，如tau蛋白和a-突触核蛋白等，副监护子CHIP与分子伴侣，如Hsc70/Hsp70、Hsp90等相互作用对这些异常蛋白的产生具有调节作用。最近研究表明，CHIP改变了Hsc70和Hsp90介导调节的信号通路中蛋白折叠和降解的平衡，参与细胞内蛋白质的质量控制；Hsp70/CHIP伴侣系统在tau蛋白生物学和tau蛋白病理学机制中具有重要作用；CHIP可以作为a-突触核蛋白蛋白酶体降解途径和溶酶体降解途径的分子开关。这些研究进展对于进一步揭示神经退行性疾病的发病机制和研制新一代治疗药物具有重要的作用。
关键词：CHIP；神经退行性疾病；异常蛋白；tau；a-突触核蛋白
Abstract: Abstract: CHIP, an E3 ubiquitin ligase and cochaperones, involves in energy metabolism and protein quality control. Aggregation and accumulation of abnormal proteins, such as tau and a-synuclein is a common pathological feature of a diverse of neurodegenerative diseases, including Alzheimer{$39}s disease (AD), Parkinson{$39}s disease (PD), and Huntington{$39}s disease (HD). Cochaperones CHIP and molecular chaperones as Hsc70/Hsp70 and Hsp90 regulate the cellular balance between aggregation and degradation of abnormal proteins. Recent studies show that CHIP apparently alters the balance between folding and degradation by cooperating with Hsc70- and Hsp90-mediated signaling pathways and plays a prominent role in protein quality control in cell. The Hsp70-CHIP chaperone system plays an important role in tau biology and in the pathogenesis of tauopathies. CHIP acts as a molecular switch between proteasomal and lysosomal degradation pathways. Disclosing of role CHIP in protein qulity control implicates attractive new targets for the development of drugs to cure neurodegenerative diseases.
Key words: CHIP; neurodegenerative disease; abnormal protein; tau; a-synuclein
