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A crazy trio in Parkinson's disease: metabolism alteration, α-synuclein aggregation, and oxidative stress

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Abstract

Parkinson's disease (PD) is an aging-associated neurodegenerative disorder, characterized by the progressive loss of dopaminergic neurons in the pars compacta of the substantia nigra and the presence of Lewy bodies containing α-synuclein within these neurons. Oligomeric α-synuclein exerts neurotoxic effects through mitochondrial dysfunction, glial cell inflammatory response, lysosomal dysfunction and so on. α-synuclein aggregation, often accompanied by oxidative stress, is generally considered to be a key factor in PD pathology. At present, emerging evidences suggest that metabolism alteration is closely associated with α-synuclein aggregation and PD progression, and improvement of key molecules in metabolism might be potentially beneficial in PD treatment. In this review, we highlight the tripartite relationship among metabolic changes, α-synuclein aggregation, and oxidative stress in PD, and offer updated insights into the treatments of PD, aiming to deepen our understanding of PD pathogenesis and explore new therapeutic strategies for the disease.

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Funding

This work was funded by National Natural Science Foundation of China (Grant No. 81600470) and Natural Science Foundation of Shandong Province (Grant No. ZR2022MC053).

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  1. These two authors have equally contributed.

Authors and Affiliations

  1. School of Basic Medicine, Qingdao University, Qingdao, China

    Sheng Li, Yanbing Liu, Sen Lu, Jiayi Xu & Yuxuan Yang

  2. Department of Biochemistry and Molecular Biology, School of Basic Medicine, Qingdao University, Qingdao, 266071, China

    Xiaokun Liu, Di Yang, Lin Hou & Ning Li

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  1. Sheng Li
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S. Li, Y. Liu and S. Lu drafted the manuscript. Y. Liu revised the manuscript for important intellectual content. S. Li revised the images. X. Liu, D. Yang, J. Xu and all other authors helped to sort out documents and revise the manuscript. N. Li conceived the work, organized, reviewed the manuscript, and made significant revisions to the drafts. All the authors approved the final manuscript.

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Li, S., Liu, Y., Lu, S. et al. A crazy trio in Parkinson's disease: metabolism alteration, α-synuclein aggregation, and oxidative stress. Mol Cell Biochem (2024). https://doi.org/10.1007/s11010-024-04985-3

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