Transthyretin Inhibits Primary and Secondary Nucleations of Amyloid-β Peptide Aggregation and Reduces the Toxicity of Its Oligomers.

ABSTRACT: Alzheimer's disease is associated with the deposition of the amyloid-β peptide (Aβ) into extracellular senile plaques in the brain. In vitro and in vivo observations have indicated that transthyretin (TTR) acts as an Aβ scavenger in the brain, but the mechanism has not been fully resolved. We have monitored the aggregation process of Aβ₄₀ by thioflavin T fluorescence, in the presence or absence of different concentrations of preformed seed aggregates of Aβ₄₀, of wild-type tetrameric TTR (WT-TTR), and of a variant engineered to be stable as a monomer (M-TTR). Both WT-TTR and M-TTR were found to inhibit specific steps of the process of Aβ₄₀ fibril formation, which are primary and secondary nucleations, without affecting the elongation of the resulting fibrils

SUBMITTER: Ghadami SA 

PROVIDER: S-EPMC7997117 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature