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

Neuroscience
H ZengJ Huang

Abstract

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.

References

Apr 6, 2000·Journal of the National Cancer Institute·M EstellerJ G Herman
Jan 10, 2002·Genes & Development·Adrian Bird
Sep 1, 2004·The Journal of Experimental Medicine·Borja G CosioPeter J Barnes
Nov 23, 2006·FEBS Letters·Keiko YazawaHachiro Sugimoto
Mar 17, 2007·Annual Review of Biochemistry·Mona D Shahbazian, Michael Grunstein
May 29, 2007·Cellular and Molecular Life Sciences : CMLS·B E MorrisonS R D'Mello
Feb 13, 2008·The Journal of Pharmacology and Experimental Therapeutics·Kyle A Rasbach, Rick G Schnellmann
May 12, 2009·Seminars in Cell & Developmental Biology·Michael WillemChristian Haass
Aug 11, 2010·Behavioral Neuroscience·Chen Chang-MuLin-Shiau Shoei-Yn
May 6, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Nobumasa TakasugiTakeshi Iwatsubo
May 27, 2011·Cancer Treatment Reviews·Till Schoofs, Carsten Müller-Tidow
Dec 29, 2011·Frontiers in Bioscience (Landmark Edition)·Regine Schneider-StockNadine Darwiche
Apr 13, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sanaz Bahari-JavanFarahnaz Sananbenesi
May 30, 2012·Nature Reviews. Genetics·Peter A Jones
Mar 2, 2013·Current Pharmaceutical Design·Min-Hsiung PanChi-Tang Ho
Oct 29, 2013·Chemical Society Reviews·Jinbo LiYan Zhang
Mar 19, 2014·Nature Reviews. Neurology·Yan-Jiang Wang
Mar 29, 2014·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Jin Kyeong Choi, Sang-Hyun Kim
May 8, 2014·Cellular and Molecular Life Sciences : CMLS·E HubinK Pauwels
Oct 14, 2014·Frontiers in Aging Neuroscience·Shraddha D RegeJeganathan Ramesh Babu
Nov 2, 2014·Scientific Reports·Yan XiangWeihui Zhou

❮ Previous
Next ❯

Related Concepts

Related Feeds

Genetics & Epigenetics of Aging

Dozens of genes are implicated in lifespan, and epigenetic changes during aging affect cell function. This feed focuses on the genetics and epigenetics of aging.

Brain Aging

Here is the latest research on intrinsic and extrinsic factors, as well as pathways and mechanisms that underlie aging in the central nervous system.

Aging Epidemiology

This feed focuses on epidemiology of aging and aging-related conditions, including Alzheimer’s disease, dementia, and age-associated cognitive impairment. Here is the latest research.

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Cell Aging (Keystone)

This feed focuses on cellular aging with emphasis on the mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.

Cell Aging

This feed focuses on cellular aging with emphasis on mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.

Age-related Dementia

Dementias are a group of conditions, including Alzheimer's disease, vascular dementia, and frontotemporal dementia, characterized by deficiencies in cognitive abilities. Age-related dementia refers to dementias that occur in older individuals, usually 60+ years old, in contrast to early-onset dementia. Follow the latest research on age-related dementia here.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.

Aging Genetics (Keystone)

This feed focuses on aging epidemiology and genetic, epigenetic, and proteomic aspects underlying aging, as well as aging- associated biomarkers. Here the latest research in this domain.