VPS35 D620N mutation impairs neurogenesis and promotes ferroptosis in Parkinson's disease by using molecular docking, molecular dynamic simulation, and cellular model.

ABSTRACT:

Backgroud

VPS35, a core component of the retromer complex, has been closely associated with neurodegenerative disorders, particularly Parkinson's disease (PD). The VPS35 D620N mutation has been identified as a pathogenic variant in familial PD. However, the precise mechanisms by which VPS35 and its D620N mutant influence neurogenesis remain poorly understood. This study explores the role of the VPS35 D620N mutation in PD-related neurogenesis.

Methods and results

Protein-protein interaction (PPI) and KEGG pathway analyses identified key regulatory molecules, including TP53, AKT1, and SRC, with the PI3K-Akt signaling pathways emerging as central contributors to mutation-induced neurogenic deficits and ferroptosis in PD. Molecular docking analysis demonstrated strong binding af

SUBMITTER: Jiang M 

PROVIDER: S-EPMC12685849 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature