Role of Lysosomal Genes for Parkinson's Pathogenesis: Insights from Molecular Mechanism to Therapeutic Strategies - PubMed
2 hours ago
- #α-Synuclein Accumulation
- #Parkinson's Therapeutics
- #Lysosomal Dysfunction
- Lysosomal dysfunction plays a critical role in Parkinson's Disease (PD) pathogenesis by contributing to α-synuclein accumulation.
- Key PD-related genes affecting lysosomal function include GBA1, LRRK2, VPS35, PRKN, PINK1, TMEM175, ATP13A2, ATP10B, and DJ-1.
- Disruption of lysosomal enzymes like cathepsins, glucocerebrosidase, galactocerebrosidase, and acid sphingomyelinase impairs the autophagic-lysosomal pathway.
- Therapeutic strategies targeting lysosomal dysfunction and α-synuclein pathology include pharmacological chaperones, immunization, enzyme replacement therapies, and small-molecule modulators.
- Combinatorial treatment approaches show promise for improving efficacy in PD, though recent clinical trials have limitations.