한빛사논문
- 조회360
Eun Hee Ahn1,2, Xia Liu1, Ashfaqul M. Alam3, Seong Su Kang1 and Keqiang Ye1,4
1Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
2Department of Physiology, College of Medicine, Hallym University, Hallymdaehak-gil, Chuncheon-si, Gangwon-Do 24252, South Korea.
3Microbiology, Immunology & Molecular Genetics, University of Kentucky, Office - MN 376, Medical Science Building, 800 Rose Street, Lexington, KY, USA.
4Faculty of Life and Health Sciences, Shenzhen Institute of Advanced Technology, Shenzhen 518055 Guangdong, China.
Corresponding authors : Correspondence to Seong Su Kang or Keqiang Ye.
Abstract
Gut dysbiosis contributes to Parkinson's disease (PD) pathogenesis. Gastrointestinal disturbances in PD patients, along with gut leakage and intestinal inflammation, take place long before motor disorders. However, it remains unknown what bacterial species in gut microbiomes play the key role in driving PD pathogenesis. Here we show that Helicobacter hepaticus (H. hepaticus), abundant in gut microbiota from rotenone-treated human α-Synuclein gene (SNCA) transgenic mice and PD patients, initiates α-Synuclein pathology and motor deficits in an AEP-dependent manner in SNCA mice. Chronic Dextran sodium sulfate (DSS) treatment, an inflammatory inducer in the gut, activates AEP (asparagine endopeptidase) that cleaves α-Synuclein N103 and triggers its aggregation, promoting inflammation in the gut and the brain and motor defects in SNCA mice. PD fecal microbiota transplant or live H. hepaticus administration into antibiotics cocktail (Abx)-pretreated SNCA mice induces α-Synuclein pathology, inflammation in the gut and brain, and motor dysfunctions, for which AEP is indispensable. Hence, Helicobacter hepaticus enriched in PD gut microbiomes may facilitate α-Synuclein pathologies and motor impairments via activating AEP.
논문정보
- Research article
- 2022년 12월 (BRIC 등록일 2023-01-03)
- 국내+국외 연구진
- 의약학 > 신경의학
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