Catechol derivatives inhibit the fibril formation of amyloid-beta peptides.
The inhibition of fibril formation of amyloid beta proteins (A beta) would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). Dopamine (DA) and other catechol derivatives were used as inhibitory factors for A beta fibril formation. The fibril formation of A beta was monitored by Thioflavin T fluorescence, a transmission electron microscopy (TEM) and a total internal reflection fluorescence microscopy (TIRFM). Catechol and its derivatives showed the dose-dependent inhibitory effects on the spontaneous A beta fibril formation. The inhibitory activity depended on the chemical structure of catechol derivatives both in the presence and absence of the liposome a model of biomembrane. Formation of catechol quinone-conjugated-A beta adduct by a Schiff-base is a key step for the inhibition effect of A beta fibril formation.
Huong
Vu Thi
VT
Division of Chemical Engineering, Department of Engineering Science, Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka 560-8531, Japan.
Shimanouchi
Toshinori
T
Shimauchi
Naoya
N
Yagi
Hisashi
H
Umakoshi
Hiroshi
H
Goto
Yuji
Y
Kuboi
Ryoichi
R
D000682:Amyloid / Q000187:drug effects* / Q000648:ultrastructure; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D052160:Benzothiazoles; D002396:Catechols / Q000737:chemistry / Q000494:pharmacology*; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D010446:Peptide Fragments / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D013844:Thiazoles / Q000737:chemistry
D000682:Amyloid; D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D002396:Catechols; D010446:Peptide Fragments; D013844:Thiazoles; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C009462:thioflavin T