Mechanisms of enhanced aggregation and fibril formation of Parkinson's disease-related variants of α-synuclein.

ABSTRACT: Aggregation of α-synuclein (α-syn) into amyloid fibrils is closely associated with Parkinson's disease (PD). Familial mutations or posttranslational truncations in α-syn are known as risk factor for PD. Here, we examined the effects of the PD-related A30P or A53T point mutation and C-terminal 123-140 or 104-140 truncation on the aggregating property of α-syn based on the kinetic and thermodynamic analyses. Thioflavin T fluorescence measurements indicated that A53T, Δ123‒140, and Δ104-140 variants aggregated faster than WT α-syn, in which the A53T mutation markedly increases nucleation rate whereas the Δ123‒140 or Δ104‒140 truncation significantly increases both nucleation and fibril elongation rates. Ultracentrifugation and western blotting analyses demonstrated that these mutations or tru

SUBMITTER: Ohgita T 

PROVIDER: S-EPMC9043213 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature