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Amyloids of α-Synuc...
Amyloids of α-Synuclein Promote Chemical Transformations of Neuronal Cell Metabolites
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- Horvath, Istvan, 1979 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Mohamed, Khadra A., 1993 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Kumar, Ranjeet, 1980 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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visa fler...
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- Wittung Stafshede, Pernilla, 1968 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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(creator_code:org_t)
- 2023
- 2023
- Engelska.
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Ingår i: International Journal of Molecular Sciences. - 1661-6596 .- 1422-0067. ; 24:16
- Relaterad länk:
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https://research.cha... (primary) (free)
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https://doi.org/10.3...
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https://research.cha...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biofysik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biophysics (hsv//eng)
Nyckelord
- Parkinson’s disease
- LC-MS
- α-synuclein
- metabolomics
- amyloid
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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