Neural Regeneration Research ›› 2025, Vol. 20 ›› Issue (1): 139-158.doi: 10.4103/NRR.NRR-D-23-01195

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The autophagy–lysosome pathway: a potential target in the chemical and gene therapeutic strategies for Parkinson’s disease

Fengjuan Jiao1, 2, *, Lingyan Meng1, Kang Du1, Xuezhi Li1, 2, *   

  1. 1School of Mental Health, Jining Medical University, Jining, Shandong Province, China; 2Shandong Collaborative Innovation Center for Diagnosis, Treatment and Behavioral Interventions of Mental Disorders, Institute of Mental Health, Jining Medical University, Jining, Shandong Province, China
  • Online:2025-01-15 Published:2025-01-15
  • Contact: Fengjuan Jiao, PhD, jiaofengjuan8516@163.com; Xuezhi Li, PhD, lixuezhi@mail.jnmc.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 82101340 (to FJ).

Abstract: Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such as α-synuclein in neurons. As one of the major intracellular degradation pathways, the autophagy-lysosome pathway plays an important role in eliminating these proteins. Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance of α-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s disease. Moreover, multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome pathway. Thus, this pathway appears to be a promising therapeutic target for treatment of Parkinson’s disease. In this review, we briefly introduce the machinery of autophagy. Then, we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome pathway. Finally, we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.

Key words: autophagy, chemical therapy, gene therapy, Parkinson’s disease, α-synuclein