Cargando…
Amyloids of α-Synuclein Promote Chemical Transformations of Neuronal Cell Metabolites
The assembly of α-synuclein into cross-β 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. Althou...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10454467/ https://www.ncbi.nlm.nih.gov/pubmed/37629028 http://dx.doi.org/10.3390/ijms241612849 |
_version_ | 1785096200793358336 |
---|---|
author | Horvath, Istvan Mohamed, Khadra A. Kumar, Ranjeet Wittung-Stafshede, Pernilla |
author_facet | Horvath, Istvan Mohamed, Khadra A. Kumar, Ranjeet Wittung-Stafshede, Pernilla |
author_sort | Horvath, Istvan |
collection | PubMed |
description | The assembly of α-synuclein into cross-β 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 α-synuclein amyloids, but not monomers, to catalyze the hydrolysis of ester and phosphoester bonds. To search for putative catalytic activity of α-synuclein amyloids on biologically relevant metabolites, we here incubated α-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 α-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 α-synuclein amyloids may be a new gain-of-function that alters the metabolite composition in cells and, thereby, modulates disease progression. |
format | Online Article Text |
id | pubmed-10454467 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-104544672023-08-26 Amyloids of α-Synuclein Promote Chemical Transformations of Neuronal Cell Metabolites Horvath, Istvan Mohamed, Khadra A. Kumar, Ranjeet Wittung-Stafshede, Pernilla Int J Mol Sci Communication The assembly of α-synuclein into cross-β 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 α-synuclein amyloids, but not monomers, to catalyze the hydrolysis of ester and phosphoester bonds. To search for putative catalytic activity of α-synuclein amyloids on biologically relevant metabolites, we here incubated α-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 α-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 α-synuclein amyloids may be a new gain-of-function that alters the metabolite composition in cells and, thereby, modulates disease progression. MDPI 2023-08-16 /pmc/articles/PMC10454467/ /pubmed/37629028 http://dx.doi.org/10.3390/ijms241612849 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Communication Horvath, Istvan Mohamed, Khadra A. Kumar, Ranjeet Wittung-Stafshede, Pernilla Amyloids of α-Synuclein Promote Chemical Transformations of Neuronal Cell Metabolites |
title | Amyloids of α-Synuclein Promote Chemical Transformations of Neuronal Cell Metabolites |
title_full | Amyloids of α-Synuclein Promote Chemical Transformations of Neuronal Cell Metabolites |
title_fullStr | Amyloids of α-Synuclein Promote Chemical Transformations of Neuronal Cell Metabolites |
title_full_unstemmed | Amyloids of α-Synuclein Promote Chemical Transformations of Neuronal Cell Metabolites |
title_short | Amyloids of α-Synuclein Promote Chemical Transformations of Neuronal Cell Metabolites |
title_sort | amyloids of α-synuclein promote chemical transformations of neuronal cell metabolites |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10454467/ https://www.ncbi.nlm.nih.gov/pubmed/37629028 http://dx.doi.org/10.3390/ijms241612849 |
work_keys_str_mv | AT horvathistvan amyloidsofasynucleinpromotechemicaltransformationsofneuronalcellmetabolites AT mohamedkhadraa amyloidsofasynucleinpromotechemicaltransformationsofneuronalcellmetabolites AT kumarranjeet amyloidsofasynucleinpromotechemicaltransformationsofneuronalcellmetabolites AT wittungstafshedepernilla amyloidsofasynucleinpromotechemicaltransformationsofneuronalcellmetabolites |