title: Vitamin D-binding protein interacts with Aβ and suppresses Aβ-mediated pathology.
abstract: The level of vitamin D-binding protein (DBP) is increased in the cerebrospinal fluid of patients with Alzheimer's disease (AD), suggesting a relationship with its pathogenesis. In this study, we investigated whether and how DBP is related to AD using several different approaches. A pull-down assay and a surface plasmon resonance binding assay indicated direct interactions between purified DBP and amyloid beta (Aβ), which was confirmed in the brain of AD patients and transgenic AD model mice by immunoprecipitation assay and immunohistochemical double-staining method. Moreover, atomic force microscopic examination revealed that DBP reduced Aβ aggregation in vitro. DBP also prevented Aβ-mediated death in cultured mouse hippocampal HT22 cell line. Finally, DBP decreased Aβ-induced synaptic loss in the hippocampus and rescued memory deficits in mice after injection of Aβ into the lateral ventricle. These results provide converging evidence that DBP attenuates the harmful effects of Aβ by a direct interaction, and suggest that DBP is a promising therapeutic agent for the treatment of AD.
authors.affiliation: Department of Biochemistry and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: M
authors.initials: M
authors.lastname: Moon
authors.forename: H
authors.initials: H
authors.lastname: Song
authors.forename: H J
authors.initials: HJ
authors.lastname: Hong
authors.forename: D W
authors.initials: DW
authors.lastname: Nam
authors.forename: M-Y
authors.initials: MY
authors.lastname: Cha
authors.forename: M S
authors.initials: MS
authors.lastname: Oh
authors.forename: J
authors.initials: J
authors.lastname: Yu
authors.forename: H
authors.initials: H
authors.lastname: Ryu
authors.forename: I
authors.initials: I
authors.lastname: Mook-Jung
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D016708:Synaptophysin / Q000378:metabolism; D014809:Vitamin D-Binding Protein / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011994:Recombinant Proteins; D016708:Synaptophysin; D014809:Vitamin D-Binding Protein; C075222:amyloid beta-protein (1-42)