P. mirabilis-derived pore-forming haemolysin, HpmA drives intestinal alpha-synuclein aggregation in a mouse model of neurodegeneration
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Le résumé fourni par la source
BACKGROUND: Recent studies suggesting the importance of the gut-microbiome in intestinal aggregated alpha synuclein (α-syn) have led to the exploration of the possible role of the gut-brain axis in central nervous system degeneration. Proteus mirabilis (P. mirabilis), a gram-negative facultative anaerobic bacterium, has been linked to brain neurodegeneration in animal studies. We hypothesised that P. mirabilis-derived virulence factors aggregate intestinal α-synuclein and could prompt the pathogenesis of dopaminergic neurodegeneration in the brain. METHODS: We used vagotomised- and antibiotic-treated male murine models to determine the pathogenesis of P. mirabilis during brain neurodegeneration. The neurodegenerative factor that is driven by P. mirabilis was determined using genetically mutated P. mirabilis. The pathological functions and interactions of the virulence factors were determined in vitro. FINDINGS: The results showed that P. mirabilis-induced motor dysfunction and neurodegeneration are regulated by intestinal α-syn aggregation in vagotomised- or antibiotic-treated murine models. We deduced that the specific virulence factor, haemolysin A (HpmA), plays a role in the pathogenesis of P. mirabilis. HpmA is involved in α-synuclein oligomerisation and membrane pore formation, resulting in the activation of mTOR-mediated autophagy signalling in intestinal neuroendocrine cells. INTERPRETATION: Taken together, the results of the present study suggest that HpmA can interact with α-syn and act as a possible indicator of brain neurodegenerative diseases that are induced by P. mirabilis. FUNDING: This study was supported by a grant from the National Research Foundation of Korea.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- P. mirabilis-derived pore-forming haemolysin, HpmA drives intestinal alpha-synuclein aggregation in a mouse model of neurodegeneration
- Date Crossref
- 01/12/2023
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Kyung Hee University Department of Biochemical and Pharmaceutical Sciences pays non établi dans la noticeUniversité ou école supérieure
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Myongji Hospital pays non établi dans la noticeÉtablissement de santé
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Hanyang University Department of Neurology pays non établi dans la noticeUniversité ou école supérieure
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Catholic University of Korea pays non établi dans la noticeUniversité ou école supérieure
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College of Pharmacy Department of Oriental Pharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute pays non établi dans la noticeUniversité ou école supérieure
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MetaCen Therapeutics Inc. R&D Center pays non établi dans la noticeEntreprise
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College of Medicine Department of Clinical Pharmacology and Therapeutics pays non établi dans la noticeUniversité ou école supérieure
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Yuseong-gu Paean Biotechnology pays non établi dans la noticeOrganisation à but non lucratif
Department of Biochemical and Pharmaceutical Sciences — Kyung Hee University, Myongji Hospital et Department of Neurology — Hanyang University, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.