Structurally distinct α-synuclein fibrils induce robust parkinsonian pathology.

ABSTRACT:

Objective

Alpha-synuclein (α-syn) is a major component of Lewy bodies, which are the pathological hallmark in Parkinson's disease, and its genetic mutations cause familial forms of Parkinson's disease. Patients with α-syn G51D mutation exhibit severe clinical symptoms. However, in vitro studies showed low propensity for α-syn with the G51D mutation. We studied the mechanisms associated with severe neurotoxicity of α-syn G51D mutation using a murine model generated by G51D α-syn fibril injection into the brain.

Methods

Structural analysis of wild-type and G51D α-syn-fibrils were performed using Fourier transform infrared spectroscopy. The ability of α-syn fibrils forming aggregates was first assessed in in vitro mammalian cells. An in vivo mouse model with an intranigral inje

SUBMITTER: Hayakawa H 

PROVIDER: S-EPMC7202333 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature