Folic Acid Inhibits Amyloid ß-Peptide Production through Modulating DNA Methyltransferase Activity in N2a-APP Cells.
Int J Mol Sci
; 16(10): 25002-13, 2015 Oct 20.
Article
in En
| MEDLINE
| ID: mdl-26492244
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 ß-peptide (Aß) 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, Aß 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 Aß protein production, whereas inhibition of DNMT activity by zebularine increased Aß production. The results indicate that folic acid induces methylation potential-dependent DNMT enzymes, thereby attenuating Aß production.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Amyloid beta-Peptides
/
Alzheimer Disease
/
Folic Acid
Limits:
Animals
/
Humans
Language:
En
Journal:
Int J Mol Sci
Year:
2015
Type:
Article
Affiliation country:
China