title: Heparin specifically inhibits binding of apolipoprotein E to amyloid beta-peptide.
abstract: Apolipoprotein E (apoE) binds to non-fibrillar amyloid beta-peptide with high affinity. We find here that heparin specifically inhibits apoE-amyloid beta-peptide (1-40) interaction. Low molecular weight heparins reduce the affinity of this interaction 3-fold as it was estimated by surface plasmon resonance. The binding is not affected by high salt concentration, which prevents heparin-induced changes of apoE conformation. We propose that rigid protein conformation, induced by high affinity heparin binding to apoE, is unfavorable for its interaction to amyloid beta-peptide. Using thioflavin T assay, we find that heparin promotes fibrillogenesis of amyloid beta-peptide whereas apoE abolishes this effect. The data suggests that the relationship between apoE and glycosaminoglycans may be important for amyloid beta-peptide fibril formation.
authors.affiliation: Centre de Médicament, Université Henri Poincaré Nancy I, 30, rue Lionnois, 54000, Nancy, France.
authors.forename: V V
authors.initials: VV
authors.lastname: Shuvaev
authors.forename: G
authors.initials: G
authors.lastname: Siest
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000187:drug effects*; D016632:Apolipoprotein A-I / Q000737:chemistry / Q000187:drug effects; D001057:Apolipoproteins E / Q000737:chemistry / Q000187:drug effects*; D001667:Binding, Competitive / Q000187:drug effects; D051152:Clusterin; D006023:Glycoproteins / Q000737:chemistry / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology; D006801:Humans; D018832:Molecular Chaperones; D010446:Peptide Fragments / Q000737:chemistry / Q000187:drug effects*; D020349:Surface Plasmon Resonance
chemical_list: D016229:Amyloid beta-Peptides; D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; C495242:CLU protein, human; D051152:Clusterin; D006023:Glycoproteins; D006495:Heparin, Low-Molecular-Weight; D018832:Molecular Chaperones; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D006493:Heparin