In:
Bulletin of the Chemical Society of Japan, Oxford University Press (OUP), Vol. 83, No. 8 ( 2010-08-15), p. 911-922
Kurzfassung:
The abnormal aggregation of tau protein into paired helical filaments (PHFs) is one of the hallmarks of Alzheimer’s disease. Although some small molecules capable of inhibiting the aggregation have been discovered, knowledge of relevant mechanisms is fragmentary. In this paper, Alzheimer’s tau fragment R3 corresponding to the third repeat of microtubule-binding domain was selected as the tau model. We, for the first time, reported flavonoids for their ability to inhibit heparin-induced assembly of R3 by thioflavin S (ThS) fluorescence assay. Moreover, we further proposed the possible inhibition mechanism of six flavonoid compounds, applying tyrosine fluorescence quenching and circular dichroism (CD) methods. It was shown that flavonoids could inhibit fibril formation of R3 by deformation of the flexible extended structure, consequently losing its aggregation ability. The inhibitory ability is closely related to their binding modes and binding degree to R3. Finally a specific flavonoid structure was found to play an important role in inhibition.
Materialart:
Online-Ressource
ISSN:
0009-2673
,
1348-0634
DOI:
10.1246/bcsj.20090254
Sprache:
Englisch
Verlag:
Oxford University Press (OUP)
Publikationsdatum:
2010
ZDB Id:
160244-5
ZDB Id:
2041163-7
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