Bile Acids\nas Modulators of α‑Synuclein\nAggregation: Implications for Parkinson’s Therapy

Parkinson’s disease (PD) is\na neurodegenerative disorder\ncharacterized by the aggregation of α-synuclein into toxic amyloid\nfibrils. Recent research suggests that bile acids altered in PD may\ninfluence their aggregation. This study investigates the effects of\nlithocholic acid (LCA) and deoxycholic acid (DCA) on α-synuclein\naggregation and toxicity. LCA significantly accelerates aggregation,\nreducing the lag phase by 75%, while DCA has a milder impact, decreasing\nthe lag phase by 30%. Binding studies show that LCA interacts with\nthe NAC region and DCA with the N-terminal region of α-synuclein.\nAggregation assays and electrophoresis reveal that LCA promotes the\nformation of toxic, SDS-resistant oligomers more effectively than\nDCA. Cytotoxicity assays confirm a lower cell viability in LCA-treated\nsamples. Additionally, combined LCA and DCA treatment results in enhanced\naggregation and toxicity, indicating a synergistic effect. These findings\nhighlight the role of bile acids in α-synuclein aggregation\nand PD pathogenesis, suggesting that targeting bile acid metabolism\ncould be a therapeutic strategy for PD.