Vitamin D-binding protein interacts with Aβ and suppresses Aβ-mediated pathology

M. Moon; H. Song; H. J. Hong; D. W. Nam; M. Y. Cha; M. S. Oh; J. Yu; H. Ryu; I. Mook-Jung

doi:10.1038/cdd.2012.161

Vitamin D-binding protein interacts with Aβ and suppresses Aβ-mediated pathology

M. Moon, H. Song, H. J. Hong, D. W. Nam, M. Y. Cha, M. S. Oh, J. Yu, H. Ryu, I. Mook-Jung

Research output: Contribution to journal › Article › peer-review

85 Citations (Scopus)

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.

Original language	English
Pages (from-to)	630-638
Number of pages	9
Journal	Cell Death and Differentiation
Volume	20
Issue number	4
DOIs	https://doi.org/10.1038/cdd.2012.161
Publication status	Published - Apr 2013

Bibliographical note

Funding Information:
Acknowledgements. This work was supported by grants from National Research Foundation 2012R1A2A1A01002881, World Class University-Neuro-cytomics (R32-10084), and the Korean National Institute of Health R&D Program Project (A092058), and supported, in part, by the Basic Research Program (2008-05943) and MRC at SNU (2011-0030738) by NRF.

Keywords

Alzheimer's disease
Amyloid beta
Cytotoxicity
Neurodegeneration
Vitamin D-binding protein

Access to Document

10.1038/cdd.2012.161

Cite this

@article{10a9c1e6921047bd91feebe6ce5596ea,

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.",

keywords = "Alzheimer's disease, Amyloid beta, Cytotoxicity, Neurodegeneration, Vitamin D-binding protein",

author = "M. Moon and H. Song and Hong, {H. J.} and Nam, {D. W.} and Cha, {M. Y.} and Oh, {M. S.} and J. Yu and H. Ryu and I. Mook-Jung",

note = "Funding Information: Acknowledgements. This work was supported by grants from National Research Foundation 2012R1A2A1A01002881, World Class University-Neuro-cytomics (R32-10084), and the Korean National Institute of Health R&D Program Project (A092058), and supported, in part, by the Basic Research Program (2008-05943) and MRC at SNU (2011-0030738) by NRF.",

year = "2013",

month = apr,

doi = "10.1038/cdd.2012.161",

language = "English",

volume = "20",

pages = "630--638",

journal = "Cell Death and Differentiation",

issn = "1350-9047",

publisher = "Springer Nature",

number = "4",

}

TY - JOUR

T1 - Vitamin D-binding protein interacts with Aβ and suppresses Aβ-mediated pathology

AU - Moon, M.

AU - Song, H.

AU - Hong, H. J.

AU - Nam, D. W.

AU - Cha, M. Y.

AU - Oh, M. S.

AU - Yu, J.

AU - Ryu, H.

AU - Mook-Jung, I.

N1 - Funding Information: Acknowledgements. This work was supported by grants from National Research Foundation 2012R1A2A1A01002881, World Class University-Neuro-cytomics (R32-10084), and the Korean National Institute of Health R&D Program Project (A092058), and supported, in part, by the Basic Research Program (2008-05943) and MRC at SNU (2011-0030738) by NRF.

PY - 2013/4

Y1 - 2013/4

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Amyloid beta

KW - Cytotoxicity

KW - Neurodegeneration

KW - Vitamin D-binding protein

UR - http://www.scopus.com/inward/record.url?scp=84874945336&partnerID=8YFLogxK

U2 - 10.1038/cdd.2012.161

DO - 10.1038/cdd.2012.161

M3 - Article

C2 - 23257976

AN - SCOPUS:84874945336

SN - 1350-9047

VL - 20

SP - 630

EP - 638

JO - Cell Death and Differentiation

JF - Cell Death and Differentiation

IS - 4

ER -

Vitamin D-binding protein interacts with Aβ and suppresses Aβ-mediated pathology

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Cite this