101 research outputs found
Epigenetics and nutrition: B-vitamin deprivation and its impact on brain amyloid
No full textEpigenetics is becoming the epicentre of modern medicine because it is beginning to clarify the relationship between genetic background, environment, aging, and disease. SAM-dependent DNA methylation at the 5-position of cytosine within CpG dinucleotides represents an important mechanism for epigenetic control of gene expression and maintenance of genome integrity. Hence, methyl deficiency leads to disturbances in gene expression. B vitamins (B12, B6, and folate) have a pivotal role in reducing homocysteine accumulation by remethylation to form methionine and by transsulfuration to form glutathione (GSH). B vitamins have therefore a central function in SAM synthesis, in gene expression, and in the synthesis of one of the major antioxidant molecules. The physiological causes of AD onset are not yet well understood, but it has been shown that changes in DNA methylation due to vitamin deficiency contributes to the basic mechanisms responsible for AD onset. Accordingly, restoration of gene methylation pattern could be a target for preventing AD or arresting the progression of disease. A methyl donor such as SAM can repair the DNA methylation pattern and thereby restore normal biological functions in AD mice. Recent studies indicate that B vitamin deprivation and SAM supplementation, which modify the SAM cycle, can influence amyloidogenesis in mice, probably via SAM-dependent methylation reactions. SAM supplementation has been shown to reduce beta amyloid in mice brain
One-carbon metabolism and Alzheimer's disease: is it all a methylation matter?
No full textThe sporadic form of Alzheimer disease, late onset Alzheimer's disease (LOAD), is a multifactorial disease; a strong link between nutritional and genetic factors with normal aging and dementia is supported by studies on nutrition, metabolism, and neurodegeneration. Specifically, the involvement of homocysteine (HCY) and its dietary determinants (vitamins B6, B12, and folate, besides methionine) in dementia has been a topic of intense investigation. In this Commentary we would like to highlight the role of 1-carbon metabolism in epigenetics and Alzheimer's disease and evidence the coinvolvement of this metabolism in amyloid and tau pathways. (C) 2011 Elsevier Inc. All rights reserved
S-adenosylmethionine and derivatives thereof for the treatment and prevention of Alzheimer Disease
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The differentiation of LS/A10 myoblast cell line (a subclone of L5 line) is controlled by changes of cultural conditions
No full textWe report here that it is possible to induce differentiation in a subline of L5 myoblast line (L5/A10) by manipulating the culture media. When L5/A10 myoblasts are cultured in F14 supplemented with 10% fetal calf serum the cells grow with a division time of 12 h and reach confluency at a cell density of approximately 2.4 x 105 cells per cm2, without undergoing differentiation, characterized, morphologically, by formation of multinucleated fibers, and biochemically, by the synthesis of muscle specific proteins such as creatinine phosphokinase or myokinase. However, cells, grown in F14 + 10% fetal calf serum, will undergo regular differentiation after a limited number of division when transferred to F14 medium supplemented with limiting concentrations (1-2%) of fetal calf serum. Investigations of the biochemistry of myoblast differentiation in cell culture will be facilitated by the availability of a cell line that can undergo differentiation under controlled conditions
Gene silencing through methylation: an epigenetic intervention on Alzheimer Disease
No full textAlzheimer disease (AD) is among the few diseases that may display high homocysteine (HCY) and low B12 and folate in blood. This observation has raised the suspect that amyloid-β overproduction and accumulation, which may be the cause of the disease, could be due to the loss of epigenetic control in the expression of the genes involved in AβPP (amyloid-β protein precursor) processing. We have shown, in cell culture, that two of the genes responsible for amyloid-β production are controlled by the methylation of their promoters. The process is strictly related to S-adenosylmethionine (SAM) metabolism. SAM is a natural compound, mainly produced by the liver, which has been found at very low concentrations in AD brains. A further support to this thesis came from the observation that in elderly DNA methylations are consistently lower than in young and mid aged people. We are actually experimenting in transgenic mice the possibility to prevent or to arrest amyloid-β accumulation, through SAM administration, and therefore its significance and the use of this drug for the treatment of the disease. © 2006 - IOS Press and the authors. All rights reserved
DNA methylase and demethylase activities are modulated by one-carbon metabolism in Alzheimer's disease models
No full textLate-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. (C) 2011 Elsevier Inc. All rights reserved
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