S-adenosylmethionine/homocysteine cycle alterations modify DNA methylation status with consequent deregulation of PS1 and BACE and beta-amyloid production

Andrea Fuso, Laura Seminara, Rosaria A. Cavallaro, Fabrizio D'Anselmi, Sigfrido Scarpa

Research output: Contribution to journalArticle

Abstract

Few diseases are characterized by high homocysteine (HCY) and low folate and vitamin B12 blood levels. Alzheimer disease (AD) is among these. It has already been shown that DNA methylation is involved in amyloid precursor protein (APP) processing and β-amyloid (Aβ) production through the regulation of Presenilin1 (PS1) expression and that exogenous S-adenosylmethionine (SAM) can silence the gene reducing Aβ production. Here we demonstrate that BACE (β-secretase), as well as PS1, is regulated by methylation and that the reduction of folate and vitamin B12 in culture medium can cause a reduction of SAM levels with consequent increase in presenilin1 and BACE levels and with increase in Aβ production. The simultaneous administration of SAM to the deficient medium can restore the normal gene expression, thus reducing the Aβ levels. The use of deprived medium was intended to mimic a mild nutritional deficit involved in the onset of AD.

Original languageEnglish
Pages (from-to)195-204
Number of pages10
JournalMolecular and Cellular Neuroscience
Volume28
Issue number1
DOIs
Publication statusPublished - Jan 2005

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience

Fingerprint Dive into the research topics of 'S-adenosylmethionine/homocysteine cycle alterations modify DNA methylation status with consequent deregulation of PS1 and BACE and beta-amyloid production'. Together they form a unique fingerprint.

  • Cite this