Effects of docosahexaenoic acid on in vitro amyloid beta peptide 25-35 fibrillation.
Amyloid beta peptide(25-35) (Abeta(25-35)) encompasses one of the neurotoxic domains of full length Abeta(1-40/42), the major proteinaceous component of amyloid deposits in Alzheimer's disease (AD). We investigated the effect of docosahexaenoic acid (DHA, 22:6, n-3), an essential brain polyunsaturated fatty acid, on the in vitro fibrillation of Abeta(25-35) and found that it significantly reduced the degree of fibrillation, as shown by a decrease in the intensity of both the thioflavin T and green fluorescence in confocal microscopy. Transmission electron microscopy revealed that DHA-incubated samples were virtually devoid of structured fibrils but had an amorphous-like consistency, whereas the controls contained structured fibers of various widths and lengths. The in vitro fibrillation of Abeta(25-35) appeared to be pH-dependent, with the strongest effect seen at pH 5.0. DHA inhibited fibrillation at all pHs, with the strongest effect at pH 7.4. It also significantly decreased the levels of Abeta(25-35) oligomers. Nonreductive gradient gel electrophoresis revealed that the molecular size of the oligomers of Abeta(25-35) was 10 kDa (equivalent to decamers of Abeta(25-35)) and that DHA dose-dependently reduced these decamers. These results suggest that DHA decreases the in vitro fibrillation of Abeta(25-35) by inhibiting the oligomeric amyloid species and, therefore, Abeta(25-35)-related neurotoxicity or behavioral impairment could be restrained by DHA.
Hashimoto
Michio
M
Department of Environmental Physiology, Shimane University Faculty of Medicine, Izumo 693-8501, Shimane, Japan. michio1@med.shimane-u.ac.jp
Shahdat
Hossain Md
HM
Katakura
Masanori
M
Tanabe
Yoko
Y
Gamoh
Shuji
S
Miwa
Koji
K
Shimada
Toshio
T
Shido
Osamu
O
D000682:Amyloid / Q000737:chemistry* / Q000187:drug effects*; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000648:ultrastructure; D052160:Benzothiazoles; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes; D006801:Humans; D066298:In Vitro Techniques; D018613:Microscopy, Confocal; D016874:Neurofibrillary Tangles / Q000187:drug effects*; D010446:Peptide Fragments / Q000737:chemistry* / Q000648:ultrastructure; D013844:Thiazoles
D000682:Amyloid; D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D005456:Fluorescent Dyes; D010446:Peptide Fragments; D013844:Thiazoles; C074636:amyloid beta-protein (25-35); C009462:thioflavin T; D004281:Docosahexaenoic Acids