tailieunhanh - Báo cáo khoa học: Docosahexaenoic acid stabilizes soluble amyloid-b protofibrils and sustains amyloid-b-induced neurotoxicity in vitro

Enrichment of diet and culture media with the polyunsaturated fatty acid docosahexaenoic acid has been found to reduce the amyloid burden in mice and lower amyloid-b(Ab) levels in both mice and cultured cells. However, the direct interaction of polyunsaturated fatty acids, such as docosahexaenoic acid, with Ab, and their effect on Abaggregation has not been explored in detail. | ễFEBS Journal Docosahexaenoic acid stabilizes soluble amyloid-b protofibrils and sustains amyloid-b-induced neurotoxicity in vitro Ann-Sofi Johansson1 Anita Garlind2 Fredrik Berglind-Dehlin1 Goran Karlsson3 Katarina Edwards3 Par Gellerfors1 Frida Ekholm-Pettersson1 Jan Palmblad4 and Lars Lannfelt1 1 Department of Public Health and Caring Sciences Uppsala University Rudbeck Laboratory Sweden 2 Neurotec Department Division of ClinicalGeriatrics Karolinska Institutet Karolinska University Hospital Huddinge Stockholm Sweden 3 Department of Physicaland AnalyticalChemistry Uppsala University Sweden 4 Department of Medicine Division of Hematology Karolinska Institutet Karolinska University Hospital Huddinge Stockholm Sweden Keywords amyloid-b docosahexaenoic acid micelles neurotoxicity protofibrils Correspondence . Johansson Department of Public Health and Caring Sciences Rudbeck Laboratory Dag Hammarskjolds vag 20 SE-75185 Uppsala Sweden Fax 46 18 4714808 Tel 46 18 4715030 E-mail Received 2 November 2006 accepted 13 December 2006 doi Enrichment of diet and culture media with the polyunsaturated fatty acid docosahexaenoic acid has been found to reduce the amyloid burden in mice and lower amyloid-b Ab levels in both mice and cultured cells. However the direct interaction of polyunsaturated fatty acids such as docosahexaenoic acid with Ab and their effect on Ab aggregation has not been explored in detail. Therefore we have investigated the effect of docosahexaenoic acid arachidonic acid and the saturated fatty acid arachidic acid on monomer oligomerization into protofibrils and protofibril fibrillization into fibrils in vitro using size exclusion chromatography. The polyunsaturated fatty acids docosahexaenoic acid and arachidonic acid at micellar concentrations stabilized soluble Ab42 wild-type protofibrils thereby hindering their conversion to insoluble fibrils. As a consequence docosahexaenoic acid .