Disassembly of amyloid beta-protein fibril by basement membrane components.
Amyloid beta-protein (A3) fibril in senile plaque may be related to the pathogenesis of Alzheimer's disease (AD). Basement membrane (BM) components are associated with the plaques in AD brain. It suggests that the BM components may play an important role in the deposition of the plaque. We investigated the potential of BM components, such as type IV collagen (collagen IV) and entactin, to induce disassembly of preformed Abeta1-42 (Abeta42) fibrils in direct comparison to laminin. Thioflavin T assays revealed that these BM components disrupted preformed Abeta42 fibrils in a dose-dependent manner. The high concentration of BM components, 100 microg/mL laminin, 50 microg/mL collagen IV and 50 microg/mL entactin, had most effect on disassembly of preformed Abeta42 fibrils (Molar ratio; Abeta42:laminin = 90:1, Abeta42:collagen IV = 34:1, Abeta42:entactin = 20:1). Circular dichroism spectroscopy data indicated that the high concentration of BM components induced structural transition in Abeta42 from beta-sheet to random structures. These results suggest that collagen IV and entactin, as well as laminin, are effective inducers of disassembly of Abeta42 fibrils. The ability of these BM components to induce random structures may be linked to the disassembly of preformed Abeta42 fibrils.
Kiuchi
Yoichi
Y
Toxicology Laboratory, Drug Metabolism and Toxicology Research Center, Taisho Pharmaceutical Co, Ltd, Saitama, Japan. yoichi.kiuchi@po.rd.taisho.co.jp
Isobe
Yoshihiko
Y
Fukushima
Kiyomi
K
Kimura
Masaaki
M
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001485:Basement Membrane / Q000737:chemistry* / Q000648:ultrastructure; D052160:Benzothiazoles; D002942:Circular Dichroism; D024141:Collagen Type IV / Q000737:chemistry / Q000494:pharmacology*; D005456:Fluorescent Dyes; D005470:Fluorometry; D006801:Humans; D007797:Laminin / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D008854:Microscopy, Electron; D013844:Thiazoles
D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D024141:Collagen Type IV; D005456:Fluorescent Dyes; D007797:Laminin; D008562:Membrane Glycoproteins; D013844:Thiazoles; C029967:nidogen; C009462:thioflavin T