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. © 2006 - IOS Press and the authors. All rights reserved.

Gene silencing through methylation: an epigenetic intervention on Alzheimer Disease / Scarpa, Sigfrido; Cavallaro, ROSARIA ADELE; D'Anselmi, Fabrizio; Fuso, Andrea. - In: JOURNAL OF ALZHEIMER'S DISEASE. - ISSN 1387-2877. - STAMPA. - 9:4(2006), pp. 407-414.

Gene silencing through methylation: an epigenetic intervention on Alzheimer Disease

SCARPA, Sigfrido;CAVALLARO, ROSARIA ADELE;D'ANSELMI, FABRIZIO;FUSO, ANDREA
2006

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. © 2006 - IOS Press and the authors. All rights reserved.
2006
Aging; Alzheimer disease; B12; Epigenomics; Folate; Gene methylation; Homocysteine; SAH; SAM
01 Pubblicazione su rivista::01a Articolo in rivista
Gene silencing through methylation: an epigenetic intervention on Alzheimer Disease / Scarpa, Sigfrido; Cavallaro, ROSARIA ADELE; D'Anselmi, Fabrizio; Fuso, Andrea. - In: JOURNAL OF ALZHEIMER'S DISEASE. - ISSN 1387-2877. - STAMPA. - 9:4(2006), pp. 407-414.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/360727
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