Lysophosphatidylcholine promoting α-Synuclein aggregation in Parkinson's disease: disrupting GCase glycosylation and lysosomal α-Synuclein degradation.

ABSTRACT: In Parkinson's Disease (PD), elevated serum lysophosphatidylcholine (LPC) levels correlate with disease progression. However, the mechanisms by which abnormal LPC elevation contributes to PD-related neurotoxicity remain poorly understood. This study aims to investigate the pathogenic role of LPC in dopaminergic neuronal damage and elucidates its underlying mechanisms. Our results showed LPC induces α-synuclein aggregation, exacerbating cognitive dysfunction. LPC activates Cleaved-Caspase3 via the orphan receptor GPR35-ERK signaling pathway, inhibits GRASP65 expression, and disrupts the polarized structure of the Golgi apparatus. This disruption impairs glycosylation and function of glucocerebrosidase (GCase), preventing its transport to lysosomes and leading to glucosylceramide (GlcCer) ac

SUBMITTER: Mu C 

PROVIDER: S-EPMC11910603 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature