Type IV collagen prevents amyloid beta-protein fibril formation.
The potential of targeting through molecular therapeutics the underlying amyloid beta-protein (A beta) fibrillogenesis causing the initiation and progression of Alzheimer's disease (AD) offers an opportunity to improve the disease. Type IV collagen (collagen IV) is localized in senile plaques in patients with AD. By using thioflavin T fluorescence spectroscopy and electron microscopy, we found that collagen IV inhibited A beta1-40 (A beta40) fibril formation. The critical concentration of collagen IV for this inhibition was 5 microg/mL. Circular dichroism data indicate that collagen IV prevents formation of a beta-structured aggregate of A beta40. These studies demonstrated that collagen IV is apparently a potent inhibitor of A beta fibril formation.
Kiuchi
Yoichi
Y
Pharmaceutical Research Laboratories, Taisho Pharmaceutical Co., Ltd., Omiya, Saitama, Japan. s14806@ccm.taisho.co.jp
Isobe
Yoshihiko
Y
Fukushima
Kiyomi
K
D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D052160:Benzothiazoles; D002942:Circular Dichroism; D024141:Collagen Type IV / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D008854:Microscopy, Electron; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D013050:Spectrometry, Fluorescence; D013844:Thiazoles / Q000378:metabolism
D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D024141:Collagen Type IV; D005456:Fluorescent Dyes; D010446:Peptide Fragments; D013844:Thiazoles; C078592:amyloid beta-protein (1-40); C009462:thioflavin T