Pathogenic Aspects and Therapeutic Avenues of Autophagy in Parkinson's Disease

Cells. 2023 Feb 15;12(4):621. doi: 10.3390/cells12040621.

Abstract

The progressive aging of the population and the fact that Parkinson's disease currently does not have any curative treatment turn out to be essential issues in the following years, where research has to play a critical role in developing therapy. Understanding this neurodegenerative disorder keeps advancing, proving the discovery of new pathogenesis-related genes through genome-wide association analysis. Furthermore, the understanding of its close link with the disruption of autophagy mechanisms in the last few years permits the elaboration of new animal models mimicking, through multiple pathways, different aspects of autophagic dysregulation, with the presence of pathological hallmarks, in brain regions affected by Parkinson's disease. The synergic advances in these fields permit the elaboration of multiple therapeutic strategies for restoring autophagy activity. This review discusses the features of Parkinson's disease, the autophagy mechanisms and their involvement in pathogenesis, and the current methods to correct this cellular pathway, from the development of animal models to the potentially curative treatments in the preclinical and clinical phase studies, which are the hope for patients who do not currently have any curative treatment.

Keywords: Parkinson’s disease; autophagy; drugs; genetic; lysosome; therapeutics.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / genetics
  • Brain / metabolism
  • Genome-Wide Association Study
  • Parkinson Disease* / metabolism

Grants and funding

R.K. is a recipient of a Clément Fayat Foundation fellowship (France). INSERM, CNRS, and the University of Bordeaux provided financial and infrastructural support. This study received financial support from the French government in the framework of the University of Bordeaux’s IdEx “Investments for the Future” program (GPR BRAIN_2030).