Artefactual source of 2-hydroxypyridine
Type | Article | ||||||||||||||||||||||||
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Date | 2022-07-26 | ||||||||||||||||||||||||
Language | English | ||||||||||||||||||||||||
Author(s) | Wilmes Paul1, 7, Trezzi Jean-Pierre1, 2, Aho Velma1, Jäger Christian1, Schade Sebastian3, 4, Janzen Annette5, Hickl Oskar1, Kunath Benoit1, Thomas Mélanie1, 6, Schmit Kristopher1, 6, Garcia Pierre1, 6, Sciortino Alessia1, 6, Martin-Gallausiaux Camille1, Halder Rashi1, Huarte Oihane Uriarte1, 6, Heurtaux Tony6, 7, Heins-Marroquin Ursula1, Gomez-Giro Gemma1, Weidenbach Katrin8, Delacour Léa1, Laczny Cédric1, Novikova Polina1, Ramiro-Garcia Javier1, Singh Randolph1, 9, Andújar Begoña Talavera1, Lebrun Laura1, Daujeumont Annegrait1, Habier Janine1, Dong Xiangyi1, Gavotto Floriane1, Heintz-Buschart Anna10, Schneider Jochen1, 11, Jehmlich Nico12, von Bergen Martin12, Schymanski Emma1, Schmitz Ruth8, Schwamborn Jens1, Glaab Enrico1, Linster Carole1, Kitami Toshimori13, Buttini Manuel1, 6, May Patrick1, Trenkwalder Claudia4, 14, Oertel Wolfgang5, Mollenhauer Brit4, 5 | ||||||||||||||||||||||||
Affiliation(s) | 1 : Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg 2 : Integrated Biobank of Luxembourg, Luxembourg Institute of Health, Dudelange, Luxembourg 3 : Department of Neurology, University Medical Center Göttingen, Göttingen, Germany 4 : Paracelsus-Elena-Klinik, Kassel, Germany 5 : Department of Neurology, Philipps-University Marburg, Marburg, Germany 6 : Luxembourg Center of Neuropathology (LCNP), Dudelange, Luxembourg 7 : Department of Life Sciences and Medicine, Faculty of Science, Technology and Medicine, University of Luxembourg, Belvaux, Luxembourg 8 : Institute for General Microbiology, Christian-Albrechts-Universität zu Kiel, Kiel, Germany 9 : Unité Contamination Chimique des Ecosystèmes Marins, IFREMER (Institut Français de Recherche pour l’Exploitation de la Mer), Nantes, France 10 : Biosystems Data Analysis, Swammerdam Institute for Life Sciences, Faculty of Science, University of Amsterdam, Amsterdam, The Netherlands 11 : Departments of Internal Medicine and Psychiatry and Psychotherapy, Saarland University Medical Center at Homburg/Saar, Homburg, Germany 12 : Helmholtz-Zentrum für Umweltforschung – UFZ GmbH, Department Molekulare Systembiologie, Leipzig, Germany 13 : RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan 14 : Department of Neurosurgery, University Medical Center Göttingen, Göttingen, Germany |
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Source | Preprint (Research Square Platform LLC), 2022-07-26 , P. 28p. | ||||||||||||||||||||||||
DOI | 10.21203/rs.3.rs-1827631/v2 | ||||||||||||||||||||||||
Note | This is a preprint ; it has not been peer reviewed by a journal | ||||||||||||||||||||||||
Abstract | 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. |
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