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 mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Systems Ecology]
Jäger, Christian mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Scientific Central Services]
Schade, Sebastian [> >]
Janzen, Annette [> >]
Hickl, Oskar mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core]
Kunath, Benoit [> >]
Thomas, Melanie mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Systems Ecology]
Schmit, Kristopher mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Systems Ecology]
Garcia, Pierre mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Neuropathology]
Sciortino, Alessia mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Neuropathology]
Martin-Gallausiaux, Camille [> >]
Halder, Rashi mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Scientific Central Services]
Huarte, Oihane Uriarte [> >]
Heurtaux, Tony mailto [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 mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > LCSB Operations]
Laczny, Cedric Christian mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Systems Ecology]
Novikova, Polina mailto [University of Luxembourg > CRC > Communication department (Communication Department)]
Ramiro-Garcia, Javier [> >]
Singh, Randolph [> >]
Andújar, Begoña Talavera [> >]
Lebrun, Laura mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Systems Ecology]
Daujeumont, Annegrait [> >]
Habier, Janine mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Systems Ecology]
Dong, Xiangyi mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Enzymology and Metabolism]
Gavotto, Floriane mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Scientific Central Services]
Heintz-Buschart, Anna [> >]
Schneider, Jochen mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Medical Translational Research]
Jehmlich, Nico [> >]
Bergen, Martin Von [> >]
Schymanski, Emma mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Environmental Cheminformatics]
Schmitz, Ruth [> >]
Schwamborn, Jens Christian mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Developmental and Cellular Biology]
Glaab, Enrico mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Biomedical Data Science]
Linster, Carole mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Enzymology and Metabolism]
Kitami, Toshimori [> >]
Buttini, Manuel mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Neuropathology]
May, Patrick mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core]
Trenkwalder, Claudia [> >]
Oertel, Wolfgang [> >]
Mollenhauer, Brit [> >]
Wilmes, Paul mailto [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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