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Author Destabilizing preformed fAbeta / tannic acid
doe

2004-12-28, 4:06 am

Biochim Biophys Acta. 2004 Nov 5;1690(3):193-202. Related Articles, Links


Anti-amyloidogenic activity of tannic acid and its activity to destabilize
Alzheimer's beta-amyloid fibrils in vitro.

Ono K, Hasegawa K, Naiki H, Yamada M.

Department of Neurology and Neurobiology of Aging, Kanazawa university Graduate
School of Medical Science, Kanazawa 920-8640, Japan.

Inhibition of the accumulation of amyloid beta-peptide (Abeta) and the
formation of beta-amyloid fibrils (fAbeta) from Abeta, as well as the
destabilization of preformed fAbeta in the CNS would be attractive therapeutic
targets for the treatment of Alzheimer's disease (AD). We previously reported
that nordihydroguaiaretic acid (NDGA) and wine-related polyphenols inhibit
fAbeta formation from Abeta(1-40) and Abeta(1-42) as well as destabilizing
preformed fAbeta(1-40) and fAbeta(1-42) dose-dependently in vitro. Using
fluorescence spectroscopic analysis with thioflavin T and electron microscopic
studies, we examined the effects of polymeric polyphenol, tannic acid (TA) on
the formation, extension, and destabilization of fAbeta(1-40) and fAbeta(1-42)
at pH 7.5 at 37 degrees C in vitro. We next compared the anti-amyloidogenic
activities of TA with myricetin, rifampicin, tetracycline, and NDGA. TA
dose-dependently inhibited fAbeta formation from Abeta(1-40) and Abeta(1-42),
as well as their extension. Moreover, it dose-dependently destabilized
preformed fAbetas. The effective concentrations (EC50) of TA for the formation,
extension and destabilization of fAbetas were in the order of 0-0.1 microM.
Although the mechanism by which TA inhibits fAbeta formation from Abeta as well
as destabilizes preformed fAbeta in vitro is still unclear, it could be a key
molecule for the development of therapeutics for AD.

PMID: 15511626 [PubMed - indexed for MEDLINE]

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