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热休克蛋白 70 与帕金森病中 Parkin 的关联

Linking Heat Shock Protein 70 and Parkin in Parkinson's Disease.

机构信息

Key Laboratory of Flexible Electronics (KLoFE) & Institute of Advanced Materials (IAM), School of Flexible Electronics (Future Technologies), Nanjing Tech University, Nanjing, 211816, People's Republic of China.

Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117054, Singapore.

出版信息

Mol Neurobiol. 2023 Dec;60(12):7044-7059. doi: 10.1007/s12035-023-03481-x. Epub 2023 Aug 1.

Abstract

Parkinson's disease (PD) is a neurodegenerative disease that affects millions of elderly people worldwide and is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The precise mechanisms underlying the pathogenesis of PD are still not fully understood, but it is well accepted that the misfolding, aggregation, and abnormal degradation of proteins are the key causative factors of PD. Heat shock protein 70 (Hsp70) is a molecular chaperone that participates in the degradation of misfolded and aggregated proteins in living cells and organisms. Parkin, an E3 ubiquitin ligase, participates in the degradation of proteins via the proteasome pathway. Recent studies have indicated that both Hsp70 and Parkin play pivotal roles in PD pathogenesis. In this review, we focus on discussing how dysregulation of Hsp70 and Parkin leads to PD pathogenesis, the interaction between Hsp70 and Parkin in the context of PD and their therapeutic applications in PD.

摘要

帕金森病(PD)是一种神经退行性疾病,影响着全球数以百万计的老年人,其特征是黑质致密部(SNpc)中的多巴胺能神经元进行性丧失。PD 发病机制的确切机制尚不完全清楚,但人们普遍认为蛋白质的错误折叠、聚集和异常降解是 PD 的关键致病因素。热休克蛋白 70(Hsp70)是一种分子伴侣,参与活细胞和生物体中错误折叠和聚集蛋白的降解。Parkin 是一种 E3 泛素连接酶,通过蛋白酶体途径参与蛋白质的降解。最近的研究表明,Hsp70 和 Parkin 都在 PD 的发病机制中发挥着关键作用。在这篇综述中,我们重点讨论了 Hsp70 和 Parkin 的失调如何导致 PD 的发病机制,以及它们在 PD 背景下的相互作用及其在 PD 中的治疗应用。

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