Effects of docosahexaenoic acid on in vitro amyloid beta peptide 25-35 fibrillation.
Biochim Biophys Acta
; 1791(4): 289-96, 2009 Apr.
Article
en En
| MEDLINE
| ID: mdl-19416653
ABSTRACT
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, 226, 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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
/
Ácidos Docosahexaenoicos
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Péptidos beta-Amiloides
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Ovillos Neurofibrilares
/
Amiloide
Límite:
Humans
Idioma:
En
Revista:
Biochim Biophys Acta
Año:
2009
Tipo del documento:
Article
País de afiliación:
Japón