中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (4): 855-862.doi: 10.4103/1673-5374.382231

• 综述:退行性病与再生 • 上一篇    下一篇

中枢神经系统中α-突触核蛋白和 tau 的病理和生理功能交叉关系

  

  • 出版日期:2024-04-15 发布日期:2023-09-15

Pathological and physiological functional cross-talks of α-synuclein and tau in the central nervous system

Mingyue Jin1, 2, *, Shengming Wang2, Xiaodie Gao1, Zhenyou Zou3, Shinji Hirotsune2, *, Liyuan Sun1, *   

  1. 1Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region, China; 2Department of Genetic Disease Research, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan; 3Department of Scientific Research, Brain Hospital of Guangxi Zhuang Autonomous Region, Liuzhou, Guangxi Zhuang Autonomous Region, China
  • Online:2024-04-15 Published:2023-09-15
  • Contact: Shinji Hirotsune, MD, PhD, shinjih@omu.ac.jp; Liyuan Sun, PhD, sunly@glmc.edu.cn; Mingyue Jin, PhD, jinmingyue@glmc.edu.cn.
  • Supported by:
    This work was supported by the Natural Science Foundation of Guangxi Zhuang Autonomous Region, Nos. 2022GXNSFAA035622 (to MJ), 2020GXNSFAA297048 (to ZZ); the National Natural Science Foundation of China, No. 82060268 (to ZZ).

摘要: https://orcid.org/0000-0002-5249-8918 (Mingyue Jin); https://orcid.org/0000-0002-5451-087X (Shinji Hirotsune); https://orcid.org/0000-0003-2529-1396 (Liyuan Sun)

Abstract: α-Synuclein and tau are abundant multifunctional brain proteins that are mainly expressed in the presynaptic and axonal compartments of neurons, respectively. Previous works have revealed that intracellular deposition of α-synuclein and/or tau causes many neurodegenerative disorders, including Alzheimer’s disease and Parkinson’s disease. Despite intense investigation, the normal physiological functions and roles of α-synuclein and tau are still unclear, owing to the fact that mice with knockout of either of these proteins do not present apparent phenotypes. Interestingly, the co-occurrence of α-synuclein and tau aggregates was found in post-mortem brains with synucleinopathies and tauopathies, some of which share similarities in clinical manifestations. Furthermore, the direct interaction of α-synuclein with tau is considered to promote the fibrillization of each of the proteins in vitro and in vivo. On the other hand, our recent findings have revealed that α-synuclein and tau are cooperatively involved in brain development in a stage-dependent manner. These findings indicate strong cross-talk between the two proteins in physiology and pathology. In this review, we provide a summary of the recent findings on the functional roles of α-synuclein and tau in the physiological conditions and pathogenesis of neurodegenerative diseases. A deep understanding of the interplay between α-synuclein and tau in physiological and pathological conditions might provide novel targets for clinical diagnosis and therapeutic strategies to treat neurodegenerative diseases.

Key words: alpha-synuclein, microtubule-associated protein, neurodegenerative disease, tau