Presenilin 1 gene silencing by S-adenosylmethionine: a treatment for Alzheimer disease?
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.
Scarpa
Sigfrido
S
Dipartimento di Chirurgia P. Valdoni, Università di Roma La Sapienza, Rome, Italy. scarpa@bce.uniroma1.it
Fuso
Andrea
A
D'Anselmi
Fabrizio
F
Cavallaro
Rosaria A
RA
D000544:Alzheimer Disease / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000096:biosynthesis*; D019175:DNA Methylation; D020868:Gene Silencing; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D008957:Models, Genetic; D053764:Presenilin-1; D012313:RNA / Q000096:biosynthesis; D012436:S-Adenosylmethionine / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D012313:RNA; D012436:S-Adenosylmethionine