Gene silencing through methylation: An epigenetic intervention on Alzheimer disease

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

Research output: Contribution to journalArticle

62 Citations (Scopus)

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-β 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 AβPP (amyloid-β protein precursor) processing. We have shown, in cell culture, that two of the genes responsible for amyloid-β 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-β accumulation, through SAM administration, and therefore its significance and the use of this drug for the treatment of the disease.

Original languageEnglish
Pages (from-to)407-414
Number of pages8
JournalJournal of Alzheimer's Disease
Volume9
Issue number4
Publication statusPublished - 2006

Fingerprint

S-Adenosylmethionine
Gene Silencing
Amyloid
Epigenomics
Methylation
Alzheimer Disease
Amyloid beta-Protein Precursor
Homocysteine
DNA Methylation
Folic Acid
Transgenic Mice
Cell Culture Techniques
Gene Expression
Liver
Brain
Pharmaceutical Preparations
Genes
Therapeutics

Keywords

  • Aging
  • Alzheimer disease
  • B12
  • Epigenomics
  • Folate
  • Gene methylation
  • Homocysteine
  • SAH
  • SAM

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology

Cite this

Scarpa, S., Cavallaro, R. A., D'Anselmi, F., & Fuso, A. (2006). Gene silencing through methylation: An epigenetic intervention on Alzheimer disease. Journal of Alzheimer's Disease, 9(4), 407-414.

Gene silencing through methylation : An epigenetic intervention on Alzheimer disease. / Scarpa, Sigfrido; Cavallaro, Rosaria A.; D'Anselmi, Fabrizio; Fuso, Andrea.

In: Journal of Alzheimer's Disease, Vol. 9, No. 4, 2006, p. 407-414.

Research output: Contribution to journalArticle

Scarpa, S, Cavallaro, RA, D'Anselmi, F & Fuso, A 2006, 'Gene silencing through methylation: An epigenetic intervention on Alzheimer disease', Journal of Alzheimer's Disease, vol. 9, no. 4, pp. 407-414.
Scarpa, Sigfrido ; Cavallaro, Rosaria A. ; D'Anselmi, Fabrizio ; Fuso, Andrea. / Gene silencing through methylation : An epigenetic intervention on Alzheimer disease. In: Journal of Alzheimer's Disease. 2006 ; Vol. 9, No. 4. pp. 407-414.
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