Galangin-induced down-regulation of BACE1 by epigenetic mechanisms in SH-SY5Y cells

• DOI: 10.1016/j.neuroscience.2015.02.054
• Publication Date: 2015-03-14T06:03:29Z
• Authors: H. Zeng; P. Huang; X. Wang; J. Wu; M. Wu; J. Huang
• Keywords: Galangin

Alzheimer's disease (AD), the most common cause of dementia in aging people, is found to have a critical link with the deposition of β-amyloid (Aβ) in the brain. The inhibition of β-site amyloid precursor protein-cleaving enzyme 1 (BACE1), a key enzyme for Aβ production, is a promising target for AD therapy. In pursuit to find a potent inhibitor of BACE1, we identified galangin, a natural flavonoid, had a significant lowering effect on Aβ levels. Furthermore, a dramatic reduction of BACE1 at mRNA and protein levels was observed after galangin treatment. We further investigated whether epigenetic mechanisms, such as histone acetylation and DNA methylation, were involved in galangin-induced transcriptional regulation of BACE1. Our data show that galangin induces a decrease of acetylated H3 in the BACE1 promoter regions through the up-regulation of endogenous HDAC1-mediated deacetylation, which is independent of DNA methylation status. The above findings suggest a novel mechanism for polyphenols' neuroprotective effect in neurodegeneration and galangin as a potential drug candidate for AD therapy.