Presenilin 1 gene silencing by S-adenosylmethionine: a treatment for Alzheimer disease?

FEBS Lett. 2003 Apr 24;541(1-3):145-8. doi: 10.1016/s0014-5793(03)00277-1.

Abstract

Presenilin 1 (PS1) is a key factor for beta-amyloid (Ab) formation in Alzheimer disease (AD). Homocysteine accumulation, frequently observed in AD patients, may be a sign of a metabolic alteration in the S-adenosylmethionine (SAM) cycle, which generates the overexpression of genes controlled by methylation of their promoters, when the cytosine in CpG moieties becomes unmethylated. The methylation of a gene involved in the processing of amyloid precursor protein may prevent Ab formation by silencing the gene. Here we report that SAM administration, in human neuroblastoma SK-N-SH cell cultures, downregulates PS1 gene expression and Ab production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / therapy
  • Amyloid beta-Peptides / biosynthesis*
  • DNA Methylation
  • Gene Silencing*
  • Humans
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / genetics*
  • Models, Genetic
  • Presenilin-1
  • RNA / biosynthesis
  • S-Adenosylmethionine / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Amyloid beta-Peptides
  • Membrane Proteins
  • PSEN1 protein, human
  • Presenilin-1
  • RNA
  • S-Adenosylmethionine