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Linking Heat Shock Protein 70 and Parkin in Parkinson’s Disease

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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.

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This work was supported by grants to Chengwu Zhang from Natural Science Foundation of Shanxi Province (#20210302123299); grant to Kahleong Lim from the Science and Technology Cooperation and Exchange Project of Shanxi Province (#202104041101026); and from the Natural Science Foundation of Jiangsu Province (BK20210544), the Postgraduate Research & Practice Innovation Program of Jiangsu Province, the Open Program of NHC Key Laboratory of Nuclear Medicine and Jiangsu Key Laboratory of Molecular Nuclear Medicine (KF202203), and the Open Project of State Key Laboratory of Coordination Chemistry.

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  1. Zhongting Zhao and Zheng Li have contributed equally to this work.

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  1. 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

    Zhongting Zhao, Fangning Du, Yue Wu, Naidi Yang & Changmin Yu

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

    Zheng Li

  3. School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China

    Yixin Wang & Chengwu Zhang

  4. Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, Singapore, 308232, Singapore

    Kah-leong Lim

  5. Institute of Flexible Electronics (IFE, Future Technologies), Xiamen University, Xiamen, 361005, People’s Republic of China

    Lin Li

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All authors contributed to the study conception and design, drafting the article, or revising it critically for important intellectual content, and approval of the final version. Zhongting Zhao and Zheng Li conceived the idea and wrote the draft. Fangning Du, Yixin Wang, and Yue Wu worked on figures and tables. Kah-leong Lim and Lin Li helped edit the manuscript. Chengwu Zhang, Changmin Yu, and Naidi Yang finalized the manuscript.

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Zhao, Z., Li, Z., Du, F. et al. Linking Heat Shock Protein 70 and Parkin in Parkinson’s Disease. Mol Neurobiol 60, 7044–7059 (2023). https://doi.org/10.1007/s12035-023-03481-x

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