The lipid peroxidation metabolite 4-oxo-2-nonenal cross-links α-synuclein causing rapid formation of stable oligomers
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- 作者：Tomas Nä ; sströ ; m ; Therese Wahlberg ; Mikael Karlsson ; Fredrik Nikolajeff ; Lars Lannfelt ; Martin Ingelsson ; Joakim Bergströ ; m
- 关键词：α ; -Synuclein ; 4-Oxo-2-nonenal ; Oligomers ; Parkinson’ ; s disease ; Dementia with Lewy bodies ; Oxidative stress
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2009
- 出版时间：23 January 2009
- 年：2009
- 卷：378
- 期：4
- 页码：872-876
- 全文大小：388 K
文摘
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 α-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 α-synuclein into 40–80 nm wide and 6–8 nm high soluble β-sheet-rich oligomers with a molecular weight of 2000 kDa. Furthermore, the ONE-induced α-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 α-synuclein molecules. Despite prolonged incubation the oligomers did not continue to aggregate into a fibrillar state, thus suggesting that these α-synuclein species were not on a fibrillogenic pathway.