First Author | Moon M | Year | 2013 |
Journal | Cell Death Differ | Volume | 20 |
Issue | 4 | Pages | 630-8 |
PubMed ID | 23257976 | Mgi Jnum | J:228264 |
Mgi Id | MGI:5705726 | Doi | 10.1038/cdd.2012.161 |
Citation | Moon M, et al. (2013) Vitamin D-binding protein interacts with Abeta and suppresses Abeta-mediated pathology. Cell Death Differ 20(4):630-8 |
abstractText | 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 (Abeta), 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 Abeta aggregation in vitro. DBP also prevented Abeta-mediated death in cultured mouse hippocampal HT22 cell line. Finally, DBP decreased Abeta-induced synaptic loss in the hippocampus and rescued memory deficits in mice after injection of Abeta into the lateral ventricle. These results provide converging evidence that DBP attenuates the harmful effects of Abeta by a direct interaction, and suggest that DBP is a promising therapeutic agent for the treatment of AD. |