Exposure to bacterial endotoxin generates a distinct strain of α-synuclein fibril. Academic Article uri icon

Overview

abstract

  • A single amyloidogenic protein is implicated in multiple neurological diseases and capable of generating a number of aggregate "strains" with distinct structures. Among the amyloidogenic proteins, α-synuclein generates multiple patterns of proteinopathies in a group of diseases, such as Parkinson disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). However, the link between specific conformations and distinct pathologies, the key concept of the strain hypothesis, remains elusive. Here we show that in the presence of bacterial endotoxin, lipopolysaccharide (LPS), α-synuclein generated a self-renewable, structurally distinct fibril strain that consistently induced specific patterns of synucleinopathies in mice. These results suggest that amyloid fibrils with self-renewable structures cause distinct types of proteinopathies despite the identical primary structure and that exposure to exogenous pathogens may contribute to the diversity of synucleinopathies.

publication date

  • August 4, 2016

Research

keywords

  • Amyloid
  • Lewy Body Disease
  • Lipopolysaccharides
  • Multiple System Atrophy
  • Parkinson Disease
  • Protein Aggregates
  • alpha-Synuclein

Identity

PubMed Central ID

  • PMC4973277

Scopus Document Identifier

  • 84982797304

Digital Object Identifier (DOI)

  • 10.1186/s12974-015-0455-9

PubMed ID

  • 27488222

Additional Document Info

volume

  • 6