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Specific interaction of VEGF 165 with β‐amyloid, and its protective effect on β‐amyloid‐induced neurotoxicity
Author(s) -
Yang SeungPil,
Kwon ByoungOh,
Gho Yong Song,
Chae ChiBom
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02993.x
Subject(s) - senile plaques , neurotoxicity , chemistry , midkine , vascular endothelial growth factor , binding site , gene isoform , amyloid (mycology) , heparin , growth factor , microbiology and biotechnology , alzheimer's disease , biochemistry , vegf receptors , cancer research , biology , medicine , receptor , toxicity , disease , inorganic chemistry , organic chemistry , gene
β‐amyloid (Aβ) is a major component of senile plaques that is commonly found in the brain of Alzheimer's disease (AD) patient. In the previous report, we showed that an important angiogenic factor, vascular endothelial growth factor (VEGF) interacts with Aβ and is accumulated in the senile plaques of AD patients' brains. Here we show that Aβ interacts with VEGF 165 isoform, but not with VEGF 121 . Aβ binds to the heparin‐binding domain (HBD) of VEGF 165 with similar affinity as that of intact VEGF 165 . Aβ binds mostly to the C‐terminal subdomain of HBD, but with greatly reduced affinity than HBD. Therefore, the full length of HBD appears to be required for maximal binding of Aβ. Although Aβ binds to heparin‐binding sequence of VEGF, it does not bind to other heparin‐binding growth factors except midkine. Thus it seems that Aβ recognizes unique structural features of VEGF HBD. VEGF 165 prevents aggregation of Aβ through its HBD. We localized the core VEGF binding site of Aβ at around 26–35 region of the peptide. VEGF 165 and HBD protect PC12 cells from the Aβ‐induced cytotoxicity. The mechanism of protection appears to be inhibition of both Aβ‐induced formation of reactive oxygen species and Aβ aggregation.