DNA methylase and demethylase activities are modulated by one-carbon metabolism in Alzheimer's disease models.
Late-onset Alzheimer's disease seems to be a multi-factorial disease with both genetic and non-genetic, environmental, possible causes. Recently, epigenomics is achieving a major role in Alzheimer's research due to its involvement in different molecular pathways leading to neurodegeneration. Among the different epigenetic modifications, DNA methylation is one of the most relevant to the disease. We previously demonstrated that presenilin1 (PSEN1), a gene involved in amyloidogenesis, is modulated by DNA methylation in neuroblastoma cells and Alzheimer's mice in an experimental model of nutritionally altered one-carbon metabolism. This alteration, obtained by nutritional deficiency of B vitamins (folate, B12 and B6) hampered S-adenosylmethionine (SAM)-dependent methylation reactions. The aim of the present paper was to investigate the regulation of DNA methylation machinery in response to hypomethylating (B vitamin deficiency) and hypermethylating (SAM supplementation) alterations of the one-carbon metabolism. We found that DNA methylases (DNMT1, 3a and 3b) and a putative demethylase (MBD2) were differently modulated, in line with the previously observed changes of PSEN1 methylation pattern in the same experimental conditions.
Fuso
Andrea
A
Department of Surgery "P. Valdoni," Sapienza University of Rome, P.le Aldo Moro, 5 - 00185, Rome, Italy. andrea.fuso@uniroma1.it
Nicolia
Vincenzina
V
Cavallaro
Rosaria A
RA
Scarpa
Sigfrido
S
D000544:Alzheimer Disease / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D002244:Carbon / Q000378:metabolism*; D002460:Cell Line; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism*; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D057890:Epigenomics; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D006801:Humans; D008297:Male; D008745:Methylation; D051379:Mice; D057507:Mice, 129 Strain; D008822:Mice, Transgenic; D012436:S-Adenosylmethionine / Q000032:analysis / Q000378:metabolism; D014805:Vitamin B 12 / Q000378:metabolism; D025101:Vitamin B 6 / Q000378:metabolism; D014803:Vitamin B Complex / Q000378:metabolism / Q000627:therapeutic use; D014804:Vitamin B Deficiency / Q000378:metabolism
D004268:DNA-Binding Proteins; C489326:Mbd2 protein, mouse; D014803:Vitamin B Complex; D002244:Carbon; D012436:S-Adenosylmethionine; D025101:Vitamin B 6; D005492:Folic Acid; D004248:DNA (Cytosine-5-)-Methyltransferases; D014805:Vitamin B 12