{"entity": "publication", "iuid": "29627f5242954b5395aae48899bdbe0b", "timestamp": "2026-09-10T23:14:46.403Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/29627f5242954b5395aae48899bdbe0b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/29627f5242954b5395aae48899bdbe0b"}}, "title": "Amyloids of \u03b1-Synuclein Promote Chemical Transformations of Neuronal Cell Metabolites.", "authors": [{"family": "Horvath", "given": "Istvan", "initials": "I", "orcid": "0000-0003-4262-1430", "researcher": {"href": "https://publications.scilifelab.se/researcher/3452a7ad90074388a30ff09f878c0b83.json"}}, {"family": "Mohamed", "given": "Khadra A", "initials": "KA"}, {"family": "Kumar", "given": "Ranjeet", "initials": "R", "orcid": "0000-0002-5859-7933", "researcher": {"href": "https://publications.scilifelab.se/researcher/34a871167fba4cea894024efbaa5c763.json"}}, {"family": "Wittung-Stafshede", "given": "Pernilla", "initials": "P", "orcid": "0000-0003-1058-1964", "researcher": {"href": "https://publications.scilifelab.se/researcher/9016aa00d62f439fb15532a1f4ba814e.json"}}], "type": "journal article", "published": "2023-08-16", "journal": {"title": "Int J Mol Sci", "issn": "1422-0067", "volume": "24", "issue": "16", "issn-l": null}, "abstract": "The assembly of \u03b1-synuclein into cross-\u03b2 structured amyloid fibers results in Lewy body deposits and neuronal degeneration in Parkinson's disease patients. As the cell environment is highly crowded, interactions between the formed amyloid fibers and a range of biomolecules can occur in cells. Although amyloid fibers are considered chemically inert species, recent in vitro work using model substrates has shown \u03b1-synuclein amyloids, but not monomers, to catalyze the hydrolysis of ester and phosphoester bonds. To search for putative catalytic activity of \u03b1-synuclein amyloids on biologically relevant metabolites, we here incubated \u03b1-synuclein amyloids with neuronal SH-SY5Y cell lysates devoid of proteins. LC-MS-based metabolomic (principal component and univariate) analysis unraveled distinct changes in several metabolite levels upon amyloid (but not monomer) incubation. Of 63 metabolites identified, the amounts of four increased (3-hydroxycapric acid, 2-pyrocatechuic acid, adenosine, and NAD), and the amounts of seventeen decreased (including aromatic and apolar amino acids, metabolites in the TCA cycle, keto acids) in the presence of \u03b1-synuclein amyloids. Many of these metabolite changes match what has been reported previously in Parkinson's disease patients and animal-model metabolomics studies. Chemical reactivity of \u03b1-synuclein amyloids may be a new gain-of-function that alters the metabolite composition in cells and, thereby, modulates disease progression.", "doi": "10.3390/ijms241612849", "pmid": "37629028", "labels": {"Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10454467"}, {"db": "pii", "key": "ijms241612849"}], "notes": [], "created": "2023-08-30T07:04:07.116Z", "modified": "2025-10-17T13:03:13.612Z"}