| Reference : An archaeal compound as a driver of Parkinson’s disease pathogenesis |
| E-prints/Working papers : Already available on another site | |||
| Life sciences : Biochemistry, biophysics & molecular biology Life sciences : Environmental sciences & ecology Life sciences : Genetics & genetic processes Life sciences : Microbiology Human health sciences : Neurology | |||
| Systems Biomedicine | |||
| http://hdl.handle.net/10993/51987 | |||
| An archaeal compound as a driver of Parkinson’s disease pathogenesis | |
| English | |
| Trezzi, Jean-Pierre [> >] | |
Aho, Velma  [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Systems Ecology] | |
| Jäger, Christian [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Scientific Central Services] | |
| Schade, Sebastian [> >] | |
| Janzen, Annette [> >] | |
| Hickl, Oskar [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core] | |
| Kunath, Benoit [> >] | |
| Thomas, Melanie [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Systems Ecology] | |
| Schmit, Kristopher [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Systems Ecology] | |
| Garcia, Pierre [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Neuropathology] | |
| Sciortino, Alessia [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Neuropathology] | |
| Martin-Gallausiaux, Camille [> >] | |
| Halder, Rashi [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Scientific Central Services] | |
| Huarte, Oihane Uriarte [> >] | |
| Heurtaux, Tony [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)] | |
| Heins-Marroquin, Ursula [> >] | |
| Gomez-Giro, Gemma [> >] | |
| Weidenbach, Katrin [> >] | |
| Delacour, Lea [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > LCSB Operations] | |
| Laczny, Cedric Christian [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Systems Ecology] | |
| Novikova, Polina [University of Luxembourg > CRC > Communication department (Communication Department)] | |
| Ramiro-Garcia, Javier [> >] | |
| Singh, Randolph [> >] | |
| Andújar, Begoña Talavera [> >] | |
| Lebrun, Laura [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Systems Ecology] | |
| Daujeumont, Annegrait [> >] | |
| Habier, Janine [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Systems Ecology] | |
| Dong, Xiangyi [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Enzymology and Metabolism] | |
| Gavotto, Floriane [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Scientific Central Services] | |
| Heintz-Buschart, Anna [> >] | |
| Schneider, Jochen [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Medical Translational Research] | |
| Jehmlich, Nico [> >] | |
| Bergen, Martin Von [> >] | |
| Schymanski, Emma [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Environmental Cheminformatics] | |
| Schmitz, Ruth [> >] | |
| Schwamborn, Jens Christian [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Developmental and Cellular Biology] | |
| Glaab, Enrico [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Biomedical Data Science] | |
| Linster, Carole [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Enzymology and Metabolism] | |
| Kitami, Toshimori [> >] | |
| Buttini, Manuel [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Neuropathology] | |
| May, Patrick [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core] | |
| Trenkwalder, Claudia [> >] | |
| Oertel, Wolfgang [> >] | |
| Mollenhauer, Brit [> >] | |
| Wilmes, Paul [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Systems Ecology >] | |
| 2022 | |
| 1 | |
| No | |
| [en] Patients with Parkinson’s disease (PD) exhibit differences in their gut microbiomes compared to healthy individuals. Although differences have most commonly been described in the abundances of bacterial taxa, changes to viral and archaeal populations have also been observed. Mechanistic links between gut microbes and PD pathogenesis remain elusive but could involve molecules that promote α-synuclein aggregation. Here, we show that 2-hydroxypyridine (2-HP) represents a key molecule for the pathogenesis of PD. We observe significantly elevated 2-HP levels in faecal samples from patients with PD or its prodrome, idiopathic REM sleep behaviour disorder (iRBD), compared to healthy controls. 2-HP is correlated with the archaeal species Methanobrevibacter smithii and with genes involved in methane metabolism, and it is detectable in isolate cultures of M. smithii. We demonstrate that 2-HP is selectively toxic to transgenic α-synuclein overexpressing yeast and increases α-synuclein aggregation in a yeast model as well as in human induced pluripotent stem cell derived enteric neurons. It also exacerbates PD-related motor symptoms, α-synuclein aggregation, and striatal degeneration when injected intrastriatally in transgenic mice overexpressing human α-synuclein. Our results highlight the effect of an archaeal molecule in relation to the gut-brain axis, which is critical for the diagnosis, prognosis, and treatment of PD. | |
| Luxembourg Centre for Systems Biomedicine (LCSB): Eco-Systems Biology (Wilmes Group) ; Luxembourg Centre for Systems Biomedicine (LCSB): Enzymology & Metabolism (Linster Group) ; Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) ; Luxembourg Centre for Systems Biomedicine (LCSB): Biomedical Data Science (Glaab Group) ; Luxembourg Centre for Systems Biomedicine (LCSB) ; Luxembourg Institute of Health - LIH ; Luxembourg Centre for Systems Biomedicine (LCSB): Medical Translational Research (J. Schneider Group) ; Luxembourg Centre for Systems Biomedicine (LCSB): Environmental Cheminformatics (Schymanski Group) ; Luxembourg Centre for Systems Biomedicine (LCSB): Developmental and Cellular Biology (Schwamborn Group) | |
| Fonds National de la Recherche - FnR ; European Research Council (ERC) ; Michael J. Fox Foundation (MJFF) | |
| Researchers ; Professionals | |
| http://hdl.handle.net/10993/51987 | |
| 10.21203/rs.3.rs-1827631/v1 | |
| https://www.researchsquare.com/article/rs-1827631/v1 | |
| https://www.researchsquare.com/article/rs-1827631/v1 | |
| FnR ; FNR11333923 > Paul Wilmes > MiBiPa > Non-invasive Microbiome-derived Multi-omic Biomarkers For The Early-stage Detection And Stratification Of Parkinson’S Disease > 01/09/2017 > 28/02/2021 > 2016 |
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