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

被引:321
作者
Fuso, A [1 ]
Seminara, L [1 ]
Cavallaro, RA [1 ]
D'Anselmi, F [1 ]
Scarpa, S [1 ]
机构
[1] Univ Roma La Sapienza, Dipartimento Chirurg P Valdoni, Lab Ric, I-00161 Rome, Italy
关键词
D O I
10.1016/j.mcn.2004.09.007
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 beta-amyloid (Abeta) production through the regulation of Presenilin1 (PS1) expression and that exogenous S-adenosylmethionine (SAM) can silence the gene reducing A production. Here we demonstrate that BACE (beta-secretase), as well as PSI, 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 Abeta production. The simultaneous administration of SAM to the deficient medium can restore the normal gene expression, thus reducing the Abeta levels. The use of deprived medium was intended to mimic a mild nutritional deficit involved in the onset of AD. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:195 / 204
页数:10
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