Galangin-induced down-regulation of BACE1 by epigenetic mechanisms in SH-SY5Y cells. - GreenMedInfo Summary
Galangin-induced down-regulation of BACE1 by epigenetic mechanisms in SH-SY5Y cells.
Neuroscience. 2015 May 21 ;294:172-81. Epub 2015 Mar 14. PMID: 25779965
Alzheimer's disease (AD), the most common cause of dementia in aging people, is found to have a critical link with the deposition ofβ-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 loweringeffect 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 ofBACE1. 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.