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

• Published in: Neural regeneration research Vol. 20; no. 1; pp. 139 - 158
• Main Authors: Jiao, Fengjuan, Meng, Lingyan, Du, Kang, Li, Xuezhi
• Format: Journal Article
• Language: English
• Published: India Medknow Publications & Media Pvt. Ltd 01.01.2025; Wolters Kluwer - Medknow; Wolters Kluwer Medknow Publications
• Subjects: autophagy; chemical therapy; gene therapy; parkinson’s disease; Review; α-synuclein
• ISSN: 1673-5374; 1876-7958
• DOI: 10.4103/NRR.NRR-D-23-01195

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.