Young rat microbiota extracts strongly inhibit fibrillation of α-synuclein and protect neuroblastoma cells and zebrafish against α-synuclein toxicity.

Autor:	Shiraz MG; Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus Centrum, Denmark., Nielsen J; Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus Centrum, Denmark., Widmann J; Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus Centrum, Denmark., Chung KHK; Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia., Davis TP; Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia., Rasmussen C; Department of Molecular Biology and Genetics, Aarhus University, Universitetsbyen 81, 8000 Aarhus Centrum, Denmark., Scavenius C; Department of Molecular Biology and Genetics, Aarhus University, Universitetsbyen 81, 8000 Aarhus Centrum, Denmark., Enghild JJ; Department of Molecular Biology and Genetics, Aarhus University, Universitetsbyen 81, 8000 Aarhus Centrum, Denmark., Martin-Gallausiaux C; Evolutionary Biology of the Microbial Cell - Biologie Evolutive de la Cellule Microbienne Institut Pasteur, 28 Rue du Docteur Roux, Paris 75724 Cedex 15, France., Singh Y; Institute of Medical Genetics and Applied Genomics, University of Tübingen, Calwerstraße 7, 72076 Tübingen, Germany; NGS Competence Centre Tübingen (NCCT), University of Tübingen, Calwerstraße 7, 72076 Tübingen, Germany., Javed I; Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia., Otzen DE; Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus Centrum, Denmark; Department of Molecular Biology and Genetics, Aarhus University, Universitetsbyen 81, 8000 Aarhus Centrum, Denmark. Electronic address: dao@inano.au.dk.
Jazyk:	angličtina
Zdroj:	Molecules and cells [Mol Cells] 2024 Nov 26; Vol. 48 (1), pp. 100161. Date of Electronic Publication: 2024 Nov 26.
DOI:	10.1016/j.mocell.2024.100161
Abstrakt:	The clinical manifestations of Parkinson's disease (PD) are driven by aggregation of α-Synuclein (α-Syn) in the brain. However, there is increasing evidence that PD may be initiated in the gut and thence spread to the brain, eg, via the vagus nerve. Many studies link PD to changes in the gut microbiome, and bacterial amyloid has been shown to stimulate α-Syn aggregation. Yet, we are not aware of any studies reporting on a direct connection between microbiome components and α-Syn aggregation. Here, we report that soluble extract from the gut microbiome of the rats, particularly young rats transgenic for PD, shows a remarkably strong ability to inhibit in vitro α-Syn aggregation and keep it natively unfolded and monomeric. The active component(s) are heat-labile molecule(s) of around 30- to 100-kDa size, which are neither nucleic acid nor lipid. Proteomic analysis identified several proteins whose concentrations in different rat samples correlated with the samples' anti-inhibitory activity, while a subsequent pull-down assay linked the protein chaperone DnaK with the inhibitory activity of young rat's microbiome, confirmed in subsequent in vitro assays. Remarkably, the microbiome extracts also protected neuroblastoma SH-SY5Y cells and zebrafish embryos against α-Syn toxicity. Our study sheds new light on the gut microbiome as a potential source of protection against PD and opens up for new microbiome-based therapeutic strategies. Competing Interests: Declaration of Competing Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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