Folic Acid Inhibits Amyloid β-Peptide Production through Modulating DNA Methyltransferase Activity in N2a-APP Cells

International Journal of Molecular Sciences

Wen Li¹  Mingyue Jiang¹  Shijing Zhao¹  Huan Liu¹  Xumei Zhang¹  John X. Wilson²  Guowei Huang¹ 

[1] Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, China; E-Mails:;Department of Exercise and Nutrition Sciences, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY 14214, USA; E-Mail:

关键词: Alzheimer’s disease;    folic acid;    DNA methyltransferases;    amyloid β-peptide;   

DOI  :  10.3390/ijms161025002

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.