Huan Liu1, Wen Li1, Shijing Zhao1, Xumei Zhang1, Meilin Zhang1, Yanyu Xiao1, John X Wilson2, Guowei Huang3. 1. Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China. 2. Department of Exercise and Nutrition Sciences, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, USA. 3. Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China. tjgwhuang@126.com.
Abstract
PURPOSE: Alzheimer's disease (AD) is a highly prevalent type of dementia. The epigenetic mechanism of gene methylation provides a putative link between nutrition, one-carbon metabolism, and disease progression because folate deficiency may cause hypomethylation of promoter regions in AD-relevant genes. We hypothesized that folic acid supplementation may protect neuron cells from amyloid β (Aβ) oligomer-induced toxicity by modulating DNA methylation of APP and PS1 in AD models. METHODS: Primary hippocampal neuronal cells and hippocampal HT-22 cells were incubated for 24 h with a combination of folic acid and either Aβ oligomers or vehicle and were then incubated for 72 h with various concentrations of folic acid. AD transgenic mice were fed either folate-deficient or control diets and gavaged daily with various doses of folic acid (0 or 600 μg/kg). DNA methyltransferase (DNMT) activity, cell viability, methylation potential of cells, APP and PS1 expression, and the methylation of the respective promoters were determined. RESULTS: Aβ oligomers lowered DNMT activity, increased PS1 and APP expression, and decreased cell viability. Folic acid dose-dependently stimulated methylation potential and DNMT activity, altered PS1 and APP promoter methylation, decreased PS1 and APP expression, and partially preserved cell viability. Folic acid increased PS1 and APP promoter methylation in AD transgenic mice. CONCLUSION: These results suggest a mechanism by which folic acid may prevent Aβ oligomer-induced neuronal toxicity.
PURPOSE:Alzheimer's disease (AD) is a highly prevalent type of dementia. The epigenetic mechanism of gene methylation provides a putative link between nutrition, one-carbon metabolism, and disease progression because folate deficiency may cause hypomethylation of promoter regions in AD-relevant genes. We hypothesized that folic acid supplementation may protect neuron cells from amyloid β (Aβ) oligomer-induced toxicity by modulating DNA methylation of APP and PS1 in AD models. METHODS: Primary hippocampal neuronal cells and hippocampal HT-22 cells were incubated for 24 h with a combination of folic acid and either Aβ oligomers or vehicle and were then incubated for 72 h with various concentrations of folic acid. ADtransgenic mice were fed either folate-deficient or control diets and gavaged daily with various doses of folic acid (0 or 600 μg/kg). DNA methyltransferase (DNMT) activity, cell viability, methylation potential of cells, APP and PS1 expression, and the methylation of the respective promoters were determined. RESULTS: Aβ oligomers lowered DNMT activity, increased PS1 and APP expression, and decreased cell viability. Folic acid dose-dependently stimulated methylation potential and DNMT activity, altered PS1 and APP promoter methylation, decreased PS1 and APP expression, and partially preserved cell viability. Folic acid increased PS1 and APP promoter methylation in ADtransgenic mice. CONCLUSION: These results suggest a mechanism by which folic acid may prevent Aβ oligomer-induced neuronal toxicity.
Authors: Heng Du; Lan Guo; Shiqiang Yan; Alexander A Sosunov; Guy M McKhann; Shirley ShiDu Yan Journal: Proc Natl Acad Sci U S A Date: 2010-10-11 Impact factor: 11.205
Authors: Jin Gao; Catherine M Cahill; Xudong Huang; Joshua L Roffman; Stefania Lamon-Fava; Maurizio Fava; David Mischoulon; Jack T Rogers Journal: Neurotherapeutics Date: 2018-01 Impact factor: 7.620