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. © 2007 - IOS Press and the authors. All rights reserved.

γ-secretase is differentially modulated by alterations of Homocysteine cycle in neuroblastoma and glioblastoma cells / Fuso, Andrea; Cavallaro, ROSARIA ADELE; Zampelli, Alessandra; D'Anselmi, Fabrizio; Piscopo, P; Scarpa, Sigfrido. - In: JOURNAL OF ALZHEIMER'S DISEASE. - ISSN 1387-2877. - STAMPA. - 11:3(2007), pp. 275-290.

γ-secretase is differentially modulated by alterations of Homocysteine cycle in neuroblastoma and glioblastoma cells.

FUSO, ANDREA;CAVALLARO, ROSARIA ADELE;ZAMPELLI, ALESSANDRA;D'ANSELMI, FABRIZIO;SCARPA, Sigfrido
2007

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. © 2007 - IOS Press and the authors. All rights reserved.
2007
01 Pubblicazione su rivista::01a Articolo in rivista
γ-secretase is differentially modulated by alterations of Homocysteine cycle in neuroblastoma and glioblastoma cells / Fuso, Andrea; Cavallaro, ROSARIA ADELE; Zampelli, Alessandra; D'Anselmi, Fabrizio; Piscopo, P; Scarpa, Sigfrido. - In: JOURNAL OF ALZHEIMER'S DISEASE. - ISSN 1387-2877. - STAMPA. - 11:3(2007), pp. 275-290.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/365766
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