Modulation of α-Synuclein Fibrillation and Toxicity by 4-Phenylbutyric Acid.

ABSTRACT: The protein misfolding and aggregation of α-synuclein (α-Syn) into neurotoxic amyloids underlies the pathogenesis of neurodegenerative diseases such as Parkinson's disease (PD). Emerging evidence suggests that 4-phenylbutyrate (PBA) may play a role as a potential chemical chaperone for targeting α-Syn aggregation, but its molecular mechanism remains largely unknown. Using in vitro assays, we demonstrate that PBA treatment alters the pattern of α-Syn aggregation, as evidenced by reduced formation of oligomeric species and its increased susceptibility to proteolytic cleavage under the influence of PBA. Proteinase K (PK) assays, surface plasmon resonance (SPR), Nile red assays, and cytotoxicity assays indicate that PBA interacts with the extensive hydrophobic contacts of α-Syn oligomers and s

SUBMITTER: Baffour K 

PROVIDER: S-EPMC11926867 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature