Changes in Presenilin 1 gene methylation pattern in diet-induced B vitamin deficiency

Fuso, Andrea; Nicolia, Vincenzina; Pasqualato, Alessia; Fiorenza, Maria Teresa; Cavallaro, Rosaria A.; Scarpa, Sigfrido

doi:10.1016/j.neurobiolaging.2009.02.013

Cited by 110 publications

(145 citation statements)

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“…Epidemiological studies have also investigated the role of the relevant B-vitamins, with the focus mainly on folate and vitamin B12. Studies involving populations with lower baseline folate status in general support the role of folate in cognitive dysfunction [160][161][162] and cognitive decline [163,164], whereas those in countries with food fortification policies and thus overall higher mean concentrations of folate, are generally less supportive for a role in cognitive dysfunction [165,166], cognitive decline [167][168][169] or dementia [170]. Similarly, a number of large cohort studies have associated low vitamin B12 status (using more sensitive biomarkers of status including MMA and HoloTC) with cognitive dysfunction [160,166,171] and cognitive decline [162,172,173] in older people.…”

Section: Brain Health In Ageingmentioning

confidence: 99%

B-Vitamins and One-Carbon Metabolism

Pentieva¹

2018

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Section: Brain Health In Ageingmentioning

confidence: 99%

B-Vitamins and One-Carbon Metabolism

Pentieva¹

2018

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“…The importance of methylations for normal brain functions is well known. It has been recently shown that alteration of one-carbon metabolism regulates expression of two key enzymes in the amyloid pathway: β-secretase (BACE1) and presenilin (PSEN1), such that low methylation potential is associated with increased Aβ production [47,[95][96]. Furthermore, activation of protein phosphatase 2A (PP2A) is SAM-dependent, and disturbed methylation status is associated with increased phosphorylation of tau, another phenomenon strictly implicated in the pathogenesis of AD [97][98].…”

Section: Involvement Of Sam In Oxidative Stress and Neurodegenerationmentioning

confidence: 99%

“…The pathogenetic model was designed to reproduce, as much as possible, one-carbon metabolism alterations caused by B vitamin deficiency, inducing exacerbation of AD-like features in TgCRND8 AD mice. These effects were counteracted by SAM supplementation, through the modulation of DNA methylation and antioxidant pathways [29,[95][96].…”

Section: Involvement Of Sam In Oxidative Stress and Neurodegenerationmentioning

confidence: 99%

“…Indeed, exogenous SAM increases plasma and brain SAM levels, balances DNA methylase/demethylase activities, restores correct PSEN1 promoter methylation [95][96] and PSEN1 and BACE1 expression, reducesβ-and γ-secretase activities and Aβ production, reduces plaques to control-like values, and improves spatial memory in B vitamin-deficient TgCRND8 mice. Finally, it has also been demonstrated that the alteration of one-carbon metabolism and redox homeostasis by B vitamin deficiency and SAM supplementation was associated to tau metabolism by restoring PP2A activity and normal Tau phosphorylation [97].…”

Section: Involvement Of Sam In Oxidative Stress and Neurodegenerationmentioning

confidence: 99%

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Role of S-adenosylmethionine in the Modulation of Oxidative Stress- Related Neurodegeneration

Cavallaro¹,

Fuso²,

D’Erme³

et al. 2016

Int J Clin Nutr Diet

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S-adenosyl-L-methionine (SAM) is the main biological methyl donor in transmethylation reactions, consisting in the transferring of a methyl moiety to different substrates including DNA, proteins, lipids and RNA. SAM level in the organism decreases with aging and restoring the original levels through exogenous supplementation is an important tool for the improvement of many vital functions. Indeed, SAM deficiency may contribute to the onset of several diseases, i.e. depression, liver diseases, osteoarthritis and senile neurological disorders such as Alzheimer's and Parkinson's diseases. Recent evidences indicate that SAM may have an involvement in oxidative stress, a process which typically involves an alteration of cellular sulfur amino acids homeostasis. SAM is not only the principal methyl donor, but also a precursor of glutathione, the major endogenous antioxidant, whose role in counteracting oxidative stress is well known. In this review we will highlight the role of SAM not just as a methyl-donor but also as a regulator of different metabolic pathways involved in the antioxidant response in brain related disorders. Role of S-adenosylmethionine in the Modulation of Oxidative StressRelated Neurodegeneration Review ArticleOpen Access IntroductionThe interaction between environmental and genetic factors plays a fundamental role in inducing and modulating the aging processes towards brain disorders. Among environmental factors, diet and nutritional lifestyle have a key role in brain health through the alteration of the intake or the bioavailability of metabolites and cofactors. Specific nutritional factors have particular impact on one-carbon metabolism, which is a complex biochemical pathway regulated by the presence of folate, vitamin B12 and B6 (among other metabolites) and leading to the production of S-adenosyl-L-methionine (SAM), the main biological methyl donor in transmethylation reactions, consisting in the transferring of a methyl moiety to different substrates including DNA, proteins, lipids and RNA. This metabolism involves three interrelated biochemical pathways: folate cycle, transsulfuration pathway and methionine cycle. These three metabolic sequences were first combined and correlated in 1964 by Laster's group [1][2][3] giving the integrated point of view of transmethylation and transsulfuration pathways, linking sulfur amino acid metabolism to the provision of methyl groups for many biochemical processes. Normal functioning of this metabolic cycle is essential for growth and development and impairment of this metabolism; transmethylation efficiency is associated with many diseases like cardiovascular diseases [4][5], liver diseases [6-9], neural tube defects [10] and brain diseases [11][12][13][14][15][16]. One-carbon metabolism alterations, low methylation and oxidative stress are all linked to Late Onset Alzheimer's Disease (LOAD) [17][18][19][20][21][22][23][24] Moreover, wide confirmed reports underline the role of SAM dependent reactions in age related neurodegeneration also showi...

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“…DNA methylation appears to play a role in human cognitive function, since mutations affecting the methylation machinery (DNMT3b) and proteins that bind to methylated DNA (MeCP2), have been shown to cause ID (20,21). Defects in DNA methylation are also thought to play a role in neurodegeneration in Alzheimer's disease, due to Alzheimer's-associated defects in the metabolism of methyl-donor molecules (22)(23)(24).…”

Section: Dna Methylation and The Formation Of Long Term And Distant Mmentioning

confidence: 99%

Epigenetic regulation of memory: implications in human cognitive disorders

Kramer

2013

BioMolecular Concepts

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Epigenetic modification of chromatin structure is an important mechanism in the regulation of gene expression. Recent studies have shown that dynamic regulation of chromatin structure occurs in response to neuronal stimulation associated with learning and memory. Learning-induced chromatin modifications include DNA methylation, histone acetylation, histone phosphorylation and histone methylation. Studies in animal models have used genetic and pharmacological methods to manipulate the epigenetic machinery in the brain during learning and memory formation. In general, these studies suggest that epigenetic regulation of chromatin structure is essential for long term memory (LTM) consolidation, which is known to require new gene transcription. Analysis of animal models has also implicated epigenetic mechanisms in impaired cognition associated with aging, neurodegenerative disease, and intellectual disability (ID). Recently, it has been shown that a subset of ID disorders and autism are caused by disruption of specific chromatin modification complexes that are involved in nuclear hormone receptor mediated transcriptional regulation. This review provides an overview of chromatin modifications that are implicated in learning and memory and discusses the role of chromatin modifying proteins in learning-induced transcriptional regulation and human cognitive disorders.

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Changes in Presenilin 1 gene methylation pattern in diet-induced B vitamin deficiency

Cited by 110 publications

References 46 publications

B-Vitamins and One-Carbon Metabolism

B-Vitamins and One-Carbon Metabolism

Role of S-adenosylmethionine in the Modulation of Oxidative Stress- Related Neurodegeneration

Epigenetic regulation of memory: implications in human cognitive disorders

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