Fast kinetics of environmentally induced α-synuclein aggregation mediated by structural alteration in NAC region and result in structure dependent cytotoxicity.

ABSTRACT: Aggregation of α-synuclein (α-syn) is associated with the manifestation of various pathogenic synucleinopathies, including Parkinson's disease attributed to both genetic and environmental stress factors. The initial events triggering α-syn aggregation and disease initiation due to environmental stress factors are still largely unknown. Here, to understand the mechanism of misfolding and aggregation initiation, we induced α-syn aggregation with rotenone, an established chemical inducer of PD like symptoms. We found that rotenone accelerates the formation of structurally distinct oligomers and fibrils that act as templates and increase the formation of conformers capable of spreading to the neighboring neuronal cells. Molecular dynamics simulations and NMR studies revealed the involvement of

SUBMITTER: Srivastava T 

PROVIDER: S-EPMC7591854 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature