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The lipid peroxidat...
The lipid peroxidation metabolite 4-oxo-2-nonenal cross-links alpha-synuclein causing rapid formation of stable oligomers
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- Näsström, Thomas (author)
- Uppsala universitet,Geriatrik
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- Wahlberg, Therese (author)
- Uppsala universitet,Geriatrik
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- Karlsson, Mikael (author)
- Uppsala universitet,Mikrosystemteknik
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- Nikolajeff, Fredrik (author)
- Uppsala universitet,Mikrosystemteknik
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- Lannfelt, Lars (author)
- Uppsala universitet,Geriatrik
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- Ingelsson, Martin (author)
- Uppsala universitet,Geriatrik
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- Bergström, Joakim (author)
- Uppsala universitet,Geriatrik
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(creator_code:org_t)
- Elsevier BV, 2009
- 2009
- English.
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In: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 378:4, s. 872-876
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Recently, the aldehyde 4-oxo-2-nonenal (ONE) was identified as a product of lipid peroxidation and found to be an effective protein modifier. In this in vitro study we investigated structural implications of the interaction between ONE and alpha-synuclein, a protein which forms intraneuronal inclusions in neurodegenerative disorders such as Parkinson's disease and dementia with Lewy bodies. Our results demonstrate that ONE induced an almost complete conversion of monomeric alpha-synuclein into 40-80 nm wide and 6-8 nm high soluble beta-sheet-rich oligomers with a molecular weight of approximately 2000 kDa. Furthermore, the ONE-induced alpha-synuclein oligomers displayed a high stability and were not sensitive to treatment with sodium dodecyl sulfate, indicating that ONE stabilized the oligomers by cross-linking individual alpha-synuclein molecules. Despite prolonged incubation the oligomers did not continue to aggregate into a fibrillar state, thus suggesting that these alpha-synuclein species were not on a fibrillogenic pathway.
Keyword
- α-Synuclein
- 4-Oxo-2-nonenal
- Oligomers
- Parkinson’s disease
- Dementia with Lewy bodies
- Oxidative stress
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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