Thermodynamic stability modulates chaperone-mediated disaggregation of α-synuclein fibrils.

ABSTRACT: Aggregation of the intrinsically disordered protein alpha-synuclein into amyloid fibrils and their subsequent intracellular accumulation are hallmark features of several neurodegenerative disorders, including Parkinson's disease, for which no curative treatments currently exist. In this study, we investigate the relationship between fibril morphology, thermodynamic stability, and susceptibility to disaggregation by the human chaperone system comprising HSP70, DNAJB1, and Apg2. By varying assembly conditions and incubation times, we generated alpha-synuclein fibrils with diverse morphological and biochemical properties, including a broad range of thermodynamic stabilities, which we quantified using a chemical depolymerization assay. The chaperone system effectively disaggregated three of th

SUBMITTER: Fricke C 

PROVIDER: S-EPMC12622358 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature