title: Gene silencing through methylation: an epigenetic intervention on Alzheimer disease.
abstract: Alzheimer disease (AD) is among the few diseases that may display high homocysteine (HCY) and low B12 and folate in blood. This observation has raised the suspect that amyloid-beta overproduction and accumulation, which may be the cause of the disease, could be due to the loss of epigenetic control in the expression of the genes involved in AbetaPP (amyloid-beta protein precursor) processing. We have shown, in cell culture, that two of the genes responsible for amyloid-beta production are controlled by the methylation of their promoters. The process is strictly related to S-adenosylmethionine (SAM) metabolism. SAM is a natural compound, mainly produced by the liver, which has been found at very low concentrations in AD brains. A further support to this thesis came from the observation that in elderly DNA methylations are consistently lower than in young and mid aged people. We are actually experimenting in transgenic mice the possibility to prevent or to arrest amyloid-beta accumulation, through SAM administration, and therefore its significance and the use of this drug for the treatment of the disease.
authors.affiliation: Department of Surgery P. Valdoni, Università di Roma La Sapienza, Via A. Scarpa 14, 00161 Rome, Italy. sigfrido.scarpa@uniroma1.it
authors.forename: Sigfrido
authors.initials: S
authors.lastname: Scarpa
authors.forename: Rosaria A
authors.initials: RA
authors.lastname: Cavallaro
authors.forename: Fabrizio
authors.initials: F
authors.lastname: D'Anselmi
authors.forename: Andrea
authors.initials: A
authors.lastname: Fuso
mesh_terms: D000375:Aging; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000235:genetics*; D020868:Gene Silencing / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D012436:S-Adenosylmethionine / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D016229:Amyloid beta-Peptides; D012436:S-Adenosylmethionine