Few diseases are characterized by high homocysteine (HCY) and low folate and vitamin B12 blood levels. Alzheimer disease (AD) is among these. It has already been shown that DNA methylation is involved in amyloid precursor protein (APP) processing and β-amyloid (Aβ) production through the regulation of Presenilin1 (PS1) expression and that exogenous S-adenosylmethionine (SAM) can silence the gene reducing Aβ production. Here we demonstrate that BACE (β-secretase), as well as PS1, is regulated by methylation and that the reduction of folate and vitamin B12 in culture medium can cause a reduction of SAM levels with consequent increase in presenilin1 and BACE levels and with increase in Aβ production. The simultaneous administration of SAM to the deficient medium can restore the normal gene expression, thus reducing the Aβ levels. The use of deprived medium was intended to mimic a mild nutritional deficit involved in the onset of AD. © 2004 Elsevier Inc. All rights reserved.

S-adenosylmethionine/homocysteine cycle alterations modify DNA methylation status with consequent deregulation of PS1 and BACE and beta-amyloid production / Fuso, Andrea; Laura, Seminara; Rosaria A., Cavallaro; D'Anselmi, Fabrizio; Scarpa, Sigfrido. - In: MOLECULAR AND CELLULAR NEUROSCIENCES. - ISSN 1044-7431. - STAMPA. - 28:1(2005), pp. 195-204. [10.1016/j.mcn.2004.09.007]

S-adenosylmethionine/homocysteine cycle alterations modify DNA methylation status with consequent deregulation of PS1 and BACE and beta-amyloid production

FUSO, ANDREA;D'ANSELMI, FABRIZIO;SCARPA, Sigfrido
2005

Abstract

Few diseases are characterized by high homocysteine (HCY) and low folate and vitamin B12 blood levels. Alzheimer disease (AD) is among these. It has already been shown that DNA methylation is involved in amyloid precursor protein (APP) processing and β-amyloid (Aβ) production through the regulation of Presenilin1 (PS1) expression and that exogenous S-adenosylmethionine (SAM) can silence the gene reducing Aβ production. Here we demonstrate that BACE (β-secretase), as well as PS1, is regulated by methylation and that the reduction of folate and vitamin B12 in culture medium can cause a reduction of SAM levels with consequent increase in presenilin1 and BACE levels and with increase in Aβ production. The simultaneous administration of SAM to the deficient medium can restore the normal gene expression, thus reducing the Aβ levels. The use of deprived medium was intended to mimic a mild nutritional deficit involved in the onset of AD. © 2004 Elsevier Inc. All rights reserved.
2005
01 Pubblicazione su rivista::01a Articolo in rivista
S-adenosylmethionine/homocysteine cycle alterations modify DNA methylation status with consequent deregulation of PS1 and BACE and beta-amyloid production / Fuso, Andrea; Laura, Seminara; Rosaria A., Cavallaro; D'Anselmi, Fabrizio; Scarpa, Sigfrido. - In: MOLECULAR AND CELLULAR NEUROSCIENCES. - ISSN 1044-7431. - STAMPA. - 28:1(2005), pp. 195-204. [10.1016/j.mcn.2004.09.007]
File allegati a questo prodotto
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/79218
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 98
  • Scopus 358
  • ???jsp.display-item.citation.isi??? 325
social impact