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Int. J. Mol. Sci. 2015, 16(10), 25002-25013; doi:10.3390/ijms161025002

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

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 14214, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Charles Brennan
Received: 29 August 2015 / Revised: 20 September 2015 / Accepted: 12 October 2015 / Published: 20 October 2015
(This article belongs to the Special Issue Amyloid-beta and Neurological Diseases)
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Abstract

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. View Full-Text
Keywords: Alzheimer’s disease; folic acid; DNA methyltransferases; amyloid β-peptide Alzheimer’s disease; folic acid; DNA methyltransferases; amyloid β-peptide
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Li, W.; Jiang, M.; Zhao, S.; Liu, H.; Zhang, X.; Wilson, J.X.; Huang, G. Folic Acid Inhibits Amyloid β-Peptide Production through Modulating DNA Methyltransferase Activity in N2a-APP Cells. Int. J. Mol. Sci. 2015, 16, 25002-25013.

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