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

Fuso, Andrea; Seminara, Laura; Cavallaro, Rosaria A.; D’Anselmi, Fabrizio; Scarpa, Sigfrido

doi:10.1016/j.mcn.2004.09.007

Cited by 365 publications

(254 citation statements)

References 43 publications

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“…The conducted studies indicate that during physiological senescence increase in Hcy concentration takes place after the age of 60 years and it may result from lowered levels of Hcy metabolism cofactors due to the physiological decrease in resistance and recuperative capacities of the body. The obtained results indicate also that the increased Hcy levels may be generated by the developing degenerative disease and this pathologic process in AD may be linked to lack of control over activity of presenilin 1 (PS1) [18].…”

Section: Discussionmentioning

confidence: 83%

Homocysteine and asymmetric dimethylarginine concentrations in the plasma of Alzheimer’s disease patients with varying degrees of dementia

Dorszewska¹,

Florczak-Wyspiańska²,

Oczkowska³

et al. 2013

AAD

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Section: Discussionmentioning

confidence: 83%

Homocysteine and asymmetric dimethylarginine concentrations in the plasma of Alzheimer’s disease patients with varying degrees of dementia

Dorszewska¹,

Florczak-Wyspiańska²,

Oczkowska³

et al. 2013

AAD

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“…12,13 Both patterns of global hypomethylation and gene-specific hypermethylation have been reported in the host genome following EBV transformation. [14][15][16][17][18][19] It has also been suggested that epigenetic modifications in cell lines may result from intrinsic factors associated with cell culturing, 4,20 including altered methylation maintenance in response to the availability of methyl donors in the culturing media, 21 and altered methylation over time with increasing passage number. 22 The observed differences in methylation between PBLs and LCLs may also be explained by cell-type specific methylation.…”

Section: Resultsmentioning

confidence: 99%

Comparative analysis of DNA methylation profiles in peripheral blood leukocytes versus lymphoblastoid cell lines

Brennan¹,

Ehrich²,

Brazil

et al. 2009

Epigenetics

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Previous reports have shown that DNA methylation profiles within primary human malignant tissues are altered when these cells are transformed into cancer cell lines. However, it is unclear if similar differences in DNA methylation profiles exist between DNA derived from peripheral blood leukocytes (PBLs) and corresponding Epstein-Barr Virus transformed lymphoblastoid cell lines (LCLs). To assess the utility of LCLs as a resource for methylation studies we have compared DNA methylation profiles in promoter and 5' regions of 318 genes in PBL and LCL sample pairs from patients with type 1 diabetes with or without nephropathy. We identified a total of 27 (~8%) genes that revealed different DNA methylation profiles in PBL compared with LCL-derived DNA samples. In conclusion, although the profiles for most promoter regions were similar between PBL-LCL pairs, our results indicate that LCL-derived DNA may not be suitable for DNA methylation studies at least in diabetic nephropathy.

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“…An in vitro study proposed that genes considered risk factors for AD are regulated by methylation [14]. The expression of BACE, as well as PS1, increased after the reduction of folate and vitamin B12 in the culture medium, with a consequent increase in Aβ production [14]. Another study published by the same group showed similar results when evaluating the effect of vitamin B deficiency in an animal model of AD [34].…”

Section: Discussionmentioning

confidence: 90%

“…However, no differences were observed in Adam10, Bace1, Bace2, Ps1, Ps2, Tace, and App expression in the hippocampi of the SD group. An in vitro study proposed that genes considered risk factors for AD are regulated by methylation [14]. The expression of BACE, as well as PS1, increased after the reduction of folate and vitamin B12 in the culture medium, with a consequent increase in Aβ production [14].…”

Section: Discussionmentioning

confidence: 99%

“…APP can be processed by α-secretases (PS1 and PS2) and γ-secretases (ADAM10 and TACE) producing non-amyloidogenic peptides, or by α-secretases and β-secretases (BACE) producing the Aβ fragments [11][12][13]. PS1 and BACE are regulated by methylation and decreased folate and vitamin B12 in culture media can cause a decrease in S-adenosylmethionine (SAM), a universal donor of methyl groups, and an increase Aβ concentration [14]. Conversely, anti-inflammatory non-steroidal therapy alters APP processing and decreases Aβ deposition in an animal model of AD [15].…”

Section: Introductionmentioning

confidence: 99%

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Hyperhomocysteinemia and Gestational Programming of Genes Involved in Alzheimer’s Disease Pathogenesis

Silva¹

2014

J Nutr Food Sci

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Sciencesda Silva et al., J Nutr Food Sci 2013, 4:1 http://dx.doi.org/10.4172/2155-9600.1000253 *Corresponding author: Vânia D'Almeida, R. Napoleão de Barros, nº 925, 3º andar, São Paulo-SP, Brazil, CEP: 04024-002, Brazil, Tel: 55-11-21490155; Fax: 55-11-55725092; E-mail: vaniadalmeida@uol.com AbstractMaternal hyperhomocysteinemia (hHcy) induced by a high methionine diet delays brain maturation and leads to impairment of learning performance in the offspring. Because methionine-homocysteine metabolism is related to the regulation of gene expression through one-carbon metabolism, we investigated whether maternal supplementation with methionine affects the expression of Adam10, Bace1, Bace2, Ps1, Ps2, Tace, App, and Tnf-α, genes related to Alzheimer's disease (AD) risk, in the offspring. Thirteen female mice were distributed into the following groups: a) standard diet and b) standard diet supplemented with 1% methionine in water. After birth, the offspring were organized into Control (CT) and Supplemented Diet (SD) groups, and at Postnatal Day (PND) 90, all animals were weighed and then euthanized. The homocysteine (Hcy) concentration in plasma was measured, and the whole brain was weighed and dissected, and the hippocampus used for gene expression analyses. A decrease in total body weight was found in SD group, but no differences in brain weight were observed. The maternal diet did not seem to affect the Hcy concentration of PND 90 offspring. No differences were found in the expression of AD related genes in the hippocampus (p>0.05). In conclusion, hHcy induced by methionine supplementation during pregnancy and lactation did not affect the expression of genes related to AD risk in the offspring.

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

Cited by 365 publications

References 43 publications

Homocysteine and asymmetric dimethylarginine concentrations in the plasma of Alzheimer’s disease patients with varying degrees of dementia

Homocysteine and asymmetric dimethylarginine concentrations in the plasma of Alzheimer’s disease patients with varying degrees of dementia

Comparative analysis of DNA methylation profiles in peripheral blood leukocytes versus lymphoblastoid cell lines

Hyperhomocysteinemia and Gestational Programming of Genes Involved in Alzheimer’s Disease Pathogenesis

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