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Sci Rep. 2016 Aug 4;6:30891. doi: 10.1038/srep30891.

Exposure to bacterial endotoxin generates a distinct strain of α-synuclein fibril.

Author information

1
Department of Biomedical Sciences, Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, Korea.
2
Departments of Neurosciences and Pathology, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
3
Department of Biochemistry, Weill Cornell Medical College, NY, USA.
4
Department of Biomedical Laboratory Science, College of Health Science, Yonsei University, Wonju, Korea.
5
Department of Neuropathology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
6
School of Chemical and Biological Engineering, College of Engineering, Seoul National University, Seoul, Korea.
7
Department of Anatomy, School of Medicine, Konkuk University, Seoul, Korea.

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.

PMID:
27488222
PMCID:
PMC4973277
DOI:
10.1038/srep30891
[Indexed for MEDLINE]
Free PMC Article

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