Exposure to bacterial endotoxin generates a distinct strain of α-synuclein fibril.
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| 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.
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| Authors | Changyoun Kim, Guohua Lv, Jun Sung Lee, Byung Chul Jung, Masami Masuda-Suzukake, Chul-Suk Hong, Elvira Valera, He-Jin Lee, Seung R Paik, Masato Hasegawa, Eliezer Masliah, David Eliezer, Seung-Jae Lee |
| Journal | Scientific reports (Sci Rep) Vol. 6 Pg. 30891 (08 04 2016) ISSN: 2045-2322 [Electronic] England |
| PMID | 27488222 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't) |
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