title: Exposure to bacterial endotoxin generates a distinct strain of α-synuclein fibril.
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.
authors.affiliation: Department of Biomedical Sciences, Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Departments of Neurosciences and Pathology, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Changyoun
authors.initials: C
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Weill Cornell Medical College, NY, USA.
authors.forename: Guohua
authors.initials: G
authors.lastname: Lv
authors.affiliation: Department of Biomedical Sciences, Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jun Sung
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences, Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Department of Biomedical Laboratory Science, College of Health Science, Yonsei University, Wonju, Korea.
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Jung
authors.affiliation: Department of Neuropathology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Masuda-Suzukake
authors.affiliation: School of Chemical and Biological Engineering, College of Engineering, Seoul National University, Seoul, Korea.
authors.forename: Chul-Suk
authors.initials: CS
authors.lastname: Hong
authors.affiliation: Departments of Neurosciences and Pathology, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Elvira
authors.initials: E
authors.lastname: Valera
authors.affiliation: Department of Anatomy, School of Medicine, Konkuk University, Seoul, Korea.
authors.forename: He-Jin
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: School of Chemical and Biological Engineering, College of Engineering, Seoul National University, Seoul, Korea.
authors.forename: Seung R
authors.initials: SR
authors.lastname: Paik
authors.affiliation: Department of Neuropathology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Hasegawa
authors.affiliation: Departments of Neurosciences and Pathology, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.affiliation: Department of Biochemistry, Weill Cornell Medical College, NY, USA.
authors.forename: David
authors.initials: D
authors.lastname: Eliezer
authors.affiliation: Department of Biomedical Sciences, Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Seung-Jae
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000473:pathology*; D008070:Lipopolysaccharides / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000378:metabolism; D019578:Multiple System Atrophy / Q000473:pathology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010300:Parkinson Disease / Q000473:pathology*; D066329:Protein Aggregates / Q000502:physiology*; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000502:physiology; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D000682:Amyloid; D008070:Lipopolysaccharides; D066329:Protein Aggregates; D051844:alpha-Synuclein