The Identification of Gyrophoric Acid, a Phytochemical Derived from Lichen, as a Potent Inhibitor for Aggregation of Amyloid Beta Peptide: In Silico and Biochemical Evaluation.

ABSTRACT: Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ) plaque accumulation and neurodegeneration. This study identified gyrophoric acid, a lichen-derived phenolic metabolite, as a dual-action Aβ42 inhibitor preventing aggregation and disassembling of mature Aβ42 fibrils. Integrated in silico studies revealed that gyrophoric acid was a strong thermodynamic stabilizer of Aβ42 (MM-GBSA: -27.3 kcal/mol) via entropically driven hydrophobic interactions and disruption of aggregation-prone conformations (100 ns MD simulations). Through biochemical analysis of the fluorescent dye thioflavin T (ThT), gyrophoric acid induced rapid Aβ42 fibril disassembly within 5 h, with time-lapse confocal microscopy quantitatively confirming the near-complete dissolution of large aggregates by 24 h. ADMET

SUBMITTER: Yang M 

PROVIDER: S-EPMC12428957 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature