Folic Acid Inhibits Amyloid β-Peptide Production through Modulating DNA Methyltransferase Activity in N2a-APP Cells.
Alzheimer's disease (AD) is a common neurodegenerative disease resulting in progressive dementia, and is a principal cause of dementia among older adults. Folate acts through one-carbon metabolism to support the methylation of multiple substrates. We hypothesized that folic acid supplementation modulates DNA methyltransferase (DNMT) activity and may alter amyloid β-peptide (Aβ) production in AD. Mouse Neuro-2a cells expressing human APP695 were incubated with folic acid (2.8-40 μmol/L), and with or without zebularine (the DNMT inhibitor). DNMT activity, cell viability, Aβ and DNMTs expression were then examined. The results showed that folic acid stimulated DNMT gene and protein expression, and DNMT activity. Furthermore, folic acid decreased Aβ protein production, whereas inhibition of DNMT activity by zebularine increased Aβ production. The results indicate that folic acid induces methylation potential-dependent DNMT enzymes, thereby attenuating Aβ production.
Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, China. liwen08648@126.com.
Wen
W
Li
Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, China. jiang2011602151@126.com.
Mingyue
M
Jiang
Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, China. zhao2011602144@126.com.
Shijing
S
Zhao
Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, China. liuhuan80@126.com.
Huan
H
Liu
Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, China. zhangxumei2013@126.com.
Xumei
X
Zhang
Department of Exercise and Nutrition Sciences, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY 14214, USA. jxwilson@buffalo.edu.
John X
JX
Wilson
Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, China. huangguowei@tmu.edu.cn.
Guowei
G
Huang
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000187:drug effects; D015254:DNA Modification Methylases / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005492:Folic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D051379:Mice
D016229:Amyloid beta-Peptides; D005492:Folic Acid; D015254:DNA Modification Methylases
Alzheimer’s disease; DNA methyltransferases; amyloid β-peptide; folic acid