摘要

Amyloid-β (Aβ) is the core component of senile plaques, which are the pathological markers for Alzheimer's disease and cerebral amyloid angiopathy. DNA methylation/demethylation plays a crucial role in gene regulation and could also be responsible for presentation of senescence. Oxidative stress, which may be induced by Aβ, is thought to be an important contributor of DNA hyper-methylation; however, contradicting this is the fact that global DNA hypo-methylation has been found in aging brains. It therefore remains largely unknown as to whether Aβ does in fact cause DNA methylation/demethylation. Neprilysin (NEP) is one of the enzymes responsible for Aβ degradation, with its expression decreasing in both Alzheimer and aging brains. Using high-performance liquid chromatography (HPLC), we explore whether Aβ is responsible for alteration of the global DNA methylation status on a murine cerebral endothelial cells model, and also use methylation-specific PCR (MSPCR) to examine whether DNA methylation status is altered on the NEP promoter region. We find that Aβ reduces global DNA methylation whilst increasing NEP DNA methylation and further suppressing the NEP expression in mRNA and protein levels. Our results support that Aβ induces epigenetic effects, implying that DNA methylation may be part of a vicious cycle involving the reduction in NEP expression along with a resultant increase in Aβ accumulation, and that Aβ may induce global DNA hypo-methylation.

原文英語
頁(從 - 到)57-61
頁數5
期刊Biochemical and Biophysical Research Communications
378
發行號1
DOIs
出版狀態已發佈 - 一月 2 2009

ASJC Scopus subject areas

  • 生物物理學
  • 生物化學
  • 分子生物學
  • 細胞生物學

指紋

深入研究「The epigenetic effects of amyloid-β<sub>1-40</sub> on global DNA and neprilysin genes in murine cerebral endothelial cells」主題。共同形成了獨特的指紋。

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