The lipid peroxidation metabolite 4-oxo-2-nonenal cross-links alpha-synuclein causing rapid formation of stable oligomers
2009 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 378, no 4, 872-876 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2009. Vol. 378, no 4, 872-876 p.
α-Synuclein, 4-Oxo-2-nonenal, Oligomers, Parkinson’s disease, Dementia with Lewy bodies, Oxidative stress
Medical and Health Sciences Engineering and Technology
IdentifiersURN: urn:nbn:se:uu:diva-111550DOI: 10.1016/j.bbrc.2008.12.005ISI: 000262447400036PubMedID: 19070597OAI: oai:DiVA.org:uu-111550DiVA: diva2:281588