The effect of S-adenosylmethionine on CNS gene expression studied by cDNA microarray analysis

Issue title: Folate and Homocysteine in Alzheimer's Disease

Guest editors: Thomas Shea

Article type: Research Article

Authors: Cavallaro, Rosaria A. | Fuso, Andrea | D'Anselmi, Fabrizio | Seminara, Laura | Scarpa, Sigfrido^{; *}

Affiliations: Department of Surgery “P. Valdoni”, Università di Roma "La Sapienza", Via A. Scarpa 14, 00161 Rome, Italy | Center for Cellular Neurobiology and Neurodegeneration Research, University of Massachusetts Lowell, Lowell, MA 01854, USA

Correspondence: [*] Corresponding author. Tel.: +39 064 9766600; Fax: +39 064 9976606; E-mail: [email protected].

Abstract: High homocysteine (Hcy) together with low S-adenosylmethionine (SAM) levels are often observed in Alzheimer disease (AD), and this could be a sign of alteration of SAM/Hcy metabolism. It has already been shown that DNA methylation is involved in amyloid-β-protein precursor (AβPP) processing and amyloid-β(Aβ) production through the regulation of Presenilin 1 (PS1) expression and that exogenous SAM can silence the gene reducing Aβ. To investigate whether SAM administration globally influenced gene expression in the brain, we analysed 588 genes of the central nervous system in SK-N-BE neuroblastoma cells, with cDNA probes derived from untreated (DM; Differentiation Medium) or SAM treated (DM+SAM) cultures. In these conditions only seven genes were modulated by SAM treatment (and therefore by DNA methylation); three were up-regulated and four down-regulated, showing low levels of modulation.

Keywords: S-adenosylmethionine, homocysteine, DNA methylation, Alzheimer's disease, gene expression

DOI: 10.3233/JAD-2006-9407

Journal: Journal of Alzheimer's Disease, vol. 9, no. 4, pp. 415-419, 2006