DNA methylase and demethylase activities are modulated by one-carbon metabolism in Alzheimer's disease models

Andrea Fuso, Vincenzina Nicolia, Rosaria A. Cavallaro, Sigfrido Scarpa

Research output: Contribution to journalArticle

Abstract

Late-onset Alzheimer's disease seems to be a multi-factorial disease with both genetic and non-genetic, environmental, possible causes. Recently, epigenomics is achieving a major role in Alzheimer's research due to its involvement in different molecular pathways leading to neurodegeneration. Among the different epigenetic modifications, DNA methylation is one of the most relevant to the disease. We previously demonstrated that presenilin1 (PSEN1), a gene involved in amyloidogenesis, is modulated by DNA methylation in neuroblastoma cells and Alzheimer's mice in an experimental model of nutritionally altered one-carbon metabolism. This alteration, obtained by nutritional deficiency of B vitamins (folate, B12 and B6) hampered S-adenosylmethionine (SAM)-dependent methylation reactions. The aim of the present paper was to investigate the regulation of DNA methylation machinery in response to hypomethylating (B vitamin deficiency) and hypermethylating (SAM supplementation) alterations of the one-carbon metabolism. We found that DNA methylases (DNMT1, 3a and 3b) and a putative demethylase (MBD2) were differently modulated, in line with the previously observed changes of PSEN1 methylation pattern in the same experimental conditions.

Original languageEnglish
Pages (from-to)242-251
Number of pages10
JournalJournal of Nutritional Biochemistry
Volume22
Issue number3
DOIs
Publication statusPublished - Mar 2011

Keywords

  • Alzheimer's Disease
  • B vitamin deficiency
  • DNA demethylase
  • DNA methylation
  • One-carbon metabolism
  • S-adenosylmethionine

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

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