Entactin-induced inhibition of human amyloid beta-protein fibril formation in vitro.
Amyloid beta-protein (Abeta) fibril in senile plaques may possibly be related to the pathogenesis of Alzheimer's disease (AD). Basement membrane (BM) components are localized to the plaques. Entactin binds the plaque associated BM components. We investigated the potential of entactin to prevent Abeta fibril formation. Thioflavin T fluorometric assay and electron microscopy revealed that entactin significantly inhibited Abeta1-40 (Abeta40) fibril formation at an Abeta40:entactin molar ratio of 50:1. The inhibitory effect of entactin was displayed in a dose-dependent manner. Circular dichroism spectroscopy data indicated that entactin induced a random coil structure in Abeta40. We propose that the ability of entactin to induce random structure is linked to the inhibition of Abeta fibril formation. Entactin may be related to the pathogenesis of AD by regulating Abeta40 fibril formation.
Kiuchi
Y
Y
Pharmacology Laboratory, Pharmaceutical Research Laboratories, Taisho Pharmaceutical Company, Limited, 403, Yoshino-cho 1-chome, Omiya, 330-8530, Saitama, Japan. s14806@taisho.co.jp
Isobe
Y
Y
Fukushima
K
K
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D002942:Circular Dichroism; D004305:Dose-Response Relationship, Drug; D005470:Fluorometry; D006801:Humans; D066298:In Vitro Techniques; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D051379:Mice; D008854:Microscopy, Electron; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure
D016229:Amyloid beta-Peptides; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C029967:nidogen