期刊
BIOCHEMISTRY
卷 45, 期 51, 页码 15610-15616出版社
AMER CHEMICAL SOC
DOI: 10.1021/bi061743l
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资金
- Medical Research Council [MC_U105178791, MC_U105184291] Funding Source: Medline
- Parkinson's UK [G-4057, G-4066] Funding Source: Medline
- MRC [MC_U105178791, MC_U105184291] Funding Source: UKRI
- Medical Research Council [MC_U105184291, MC_U105178791] Funding Source: researchfish
alpha-Synuclein is a small cytosolic protein involved in the pathogenesis of Parkinson's disease and other neurodegenerative disorders. Recent studies suggested a lipid-related function for this brain-enriched protein. Since the brain carries a high level of docosahexaenoic acid (DHA) and since the extent of alpha-synuclein gene expression increases in response to DHA intake, we have investigated the interaction of alpha-synuclein with this essential omega-3 fatty acid. We show that alpha-synuclein allows DHA to be present in a soluble rather than micellar form. Upon interaction with DHA, the normally unstructured alpha-synuclein rapidly adopts an alpha-helical conformation. Prolonged exposure to DHA, however, gradually converts alpha-synuclein into amyloid-like fibrils. These results identify a potential biological function for alpha-synuclein and define an omega-3-linked pathway leading to alpha-synuclein aggregation.
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