Autophagy impairment in Parkinson’s disease: approaches to therapy
- Authors: Usenko T.S.1,2
-
Affiliations:
- Petersburg Nuclear Physics Institute named by B.P. Konstantinov of National Research Centre “Kurchatov Institute”
- Pavlov First Saint-Petersburg State Medical University
- Issue: Vol 59, No 1 (2025)
- Pages: 60-79
- Section: ОБЗОРЫ
- URL: https://rjpbr.com/0026-8984/article/view/682230
- DOI: https://doi.org/10.31857/S0026898425010053
- EDN: https://elibrary.ru/HDEMSA
- ID: 682230
Cite item
Abstract
Parkinson's disease (PD) is one of the most common neurodegenerative disorders characterized by progressive motor impairment due to the death of dopaminergic neurons in the substantia nigra of the brain. PD affects more than 1% of the population over 60 years of age worldwide. Despite significant progress in understanding the pathogenesis of PD, including genetic and biochemical aspects, current therapies are limited to symptomatic treatment. Recent evidence suggests that impaired autophagy leads to the accumulation of abnormal proteins, particularly α-synuclein, aggregated forms of which are neurotoxic to dopaminergic neurons in the substantia nigra. Notably, PD is predominantly sporadic. However, monogenic forms of the disease have also been described. Among the most common PD forms with known etiology are PD associated with mutations in the GBA1 gene and PD associated with mutations in the LRRK2 gene. Leucine-rich repeat kinase 2 (LRRK2), encoded by the LRRK2 gene, and the lysosomal enzyme glucocerebrosidase (GCase), encoded by the GBA1 gene, are involved in the same endolysosomal pathway. The LRRK2 and GCase dysfunction reported in PD, especially in the case of mutations in the genes encoding them, can lead to impairment of the endolysosomal pathway, lysosomal function, and possibly autophagy. This review highlights the molecular mechanisms of autophagy and prospects for targeted therapy of PD based on the induction of autophagy by influencing key players in this process.
Keywords
Full Text

About the authors
T. S. Usenko
Petersburg Nuclear Physics Institute named by B.P. Konstantinov of National Research Centre “Kurchatov Institute”; Pavlov First Saint-Petersburg State Medical University
Author for correspondence.
Email: usenko_ts@pnpi.nrcki.ru
Russian Federation, Gatchina; Saint-Petersburg
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