Entactin-induced inhibition of human amyloid β-protein fibril formation in vitro

• Published in: Neuroscience letters 2001-06, Vol.305 (2), p.119-122
• Main Authors: Kiuchi, Yoichi, Isobe, Yoshihiko, Fukushima, Kiyomi
• Format: Article
• Language: English
• Subjects: Alzheimer’s disease; Amyloid beta-Peptides - antagonists & inhibitors; Amyloid beta-Peptides - drug effects; Amyloid beta-Peptides - physiology; Amyloid beta-Peptides - ultrastructure; Amyloid β-protein; Animals; Basement membrane; Biological and medical sciences; Chemical Phenomena; Chemistry; Circular Dichroism; Circular dichroism spectroscopy; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dose-Response Relationship, Drug; Electron microscopy; Entactin; Extracellular matrix; Fluorometry; Humans; In Vitro Techniques; Medical sciences; Membrane Glycoproteins - pharmacology; Mice; Microscopy, Electron; Neurology; Peptide Fragments - antagonists & inhibitors; Peptide Fragments - drug effects; Peptide Fragments - physiology; Peptide Fragments - ultrastructure; Thioflavin T
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/S0304-3940(01)01831-6

Amyloid β-protein (Aβ) 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 Aβ fibril formation. Thioflavin T fluorometric assay and electron microscopy revealed that entactin significantly inhibited Aβ1–40 (Aβ40) fibril formation at an Aβ40: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 Aβ40. We propose that the ability of entactin to induce random structure is linked to the inhibition of Aβ fibril formation. Entactin may be related to the pathogenesis of AD by regulating Aβ40 fibril formation.