Affiliations: [a] Department of Surgery “P. Valdoni”, University of Rome “La Sapienza”, Rome, Italy | [b] Section of Degenerative Inflammatory and Neurological Disease, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Roma, Italy
Correspondence:
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Corresponding author: Sigfrido Scarpa, Via A. Scarpa, 14, 00161 – Roma, Italy. Tel.: +390649766600; Fax: +390649766606; E-mail: sigfrido.scarpa@uniroma1.it
Abstract: Multiple aspects of homocysteine metabolism were studied to understand the mechanism responsible for hyperhomocysteinemia toxicity in Alzheimer disease. Besides oxidative stress and vascular damage, homocysteine has also a great importance in regulating DNA methylation through S-adenosylmethionine, the main methyl donor in eukaryotes. Alterations of S-adenosylmethionine and methylation were evidenced in Alzheimer disease and in elderly. In order to clarify whether DNA methylation can provide the basis for amyloid-β overproduction, we used human SK-N-BE neuroblastoma and A172 glioblastoma cell lines. We tested the effects of folate, B12 and B6 deprivation and S-adenosylmethionine addition on methylation metabolism. Our results indicate that homocysteine accumulation induced through vitamin B deprivation could impair the “Methylation Potential” with consequent presenilin 1, BACE and amyloid-β upregulation. Moreover, we found that homocysteine alterations had an effect on neuroblastoma but not on glioblastoma cells; this suggests a possible differential role of the two cell types in Alzheimer disease.
