The α-Synuclein Monomer May Have Different Misfolding Mechanisms in the Induction of α-Synuclein Fibrils with Different Polymorphs.

ABSTRACT: The aggregation of alpha-synuclein (α-Syn) is closely related to the occurrence of some neurodegenerative diseases such as Parkinson's disease. The misfolding of α-Syn monomer plays a key role in the formation of aggregates and extension of fibril. However, the misfolding mechanism of α-Syn remains elusive. Here, three different α-Syn fibrils (isolated from a diseased human brain, generated by in vitro cofactor-tau induction, and obtained by in vitro cofactor-free induction) were selected for the study. The misfolding mechanisms of α-Syn were uncovered by studying the dissociation of the boundary chains based on the conventional molecular dynamics (MD) and Steered MD simulations. The results showed that the dissociation paths of the boundary chains in the three systems were different. Acco

SUBMITTER: Zhao N 

PROVIDER: S-EPMC10136287 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature