Presenilin 1 gene silencing by S‐adenosylmethionine: a treatment for Alzheimer disease?

FEBS Letters

Fuso, Andrea¹  Scarpa, Sigfrido¹  Cavallaro, Rosaria A¹  D'Anselmi, Fabrizio¹ 

[1] Dipartimento di Chirurgia ‘P. Valdoni’, Università di Roma ‘La Sapienza’, via A. Scarpa 14, 00161 Rome, Italy

关键词: Alzheimer disease;    β-Amyloid;    DNA methylation;    Presenilin 1;    Homocysteine;    S-Adenosylmethionine;    AD;    Alzheimer disease;    Ab;    β-amyloid peptide;    APP;    amyloid precursor protein;    PS1;    presenilin 1;    PS2;    presenilin 2;    SAM;    S-adenosylmethionine;   

DOI  :  10.1016/S0014-5793(03)00277-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Presenilin 1 (PS1) is a key factor for β-amyloid (Ab) formation in Alzheimer disease (AD). Homocysteine accumulation, frequently observed in AD patients, may be a sign of a metabolic alteration in the S-adenosylmethionine (SAM) cycle, which generates the overexpression of genes controlled by methylation of their promoters, when the cytosine in CpG moieties becomes unmethylated. The methylation of a gene involved in the processing of amyloid precursor protein may prevent Ab formation by silencing the gene. Here we report that SAM administration, in human neuroblastoma SK-N-SH cell cultures, downregulates PS1 gene expression and Ab production.

【 授权许可】

Unknown