S-adenosylmethionine reduces the progress of the Alzheimer-like features induced by B-vitamin deficiency in mice

Fuso, Andrea; Nicolia, Vincenzina; Ricceri, Laura; Cavallaro, Rosaria A.; Isopi, Elisa; Mangia, Franco; Fiorenza, Maria Teresa; Scarpa, Sigfrido

doi:10.1016/j.neurobiolaging.2011.12.013

Cited by 115 publications

(82 citation statements)

References 60 publications

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“…It has been observed, contrary to expectations, that the removal of amyloid plaques did not improve cognitive function [28]. If the hypothesis proposed in this paper has some validity, it may be more appropriate to focus on increasing brain concentration of S-adenosylmethionine [29], which is commercially available in nutrition centers, since low brain concentration has been associated with irreversible changes in cognitive function.…”

Section: An Approach In the Development Of Ad Therapymentioning

confidence: 77%

Alzheimer’s Disease: Adult-Onset of Inborn Error of Methionine Metabolism

2018

J Parkinsons Dis Alzheimers Dis

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Section: An Approach In the Development Of Ad Therapymentioning

confidence: 77%

Alzheimer’s Disease: Adult-Onset of Inborn Error of Methionine Metabolism

2018

J Parkinsons Dis Alzheimers Dis

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“…Because of this lack of scientific evidences it has been questioned whether SAM crosses cell membrane and/or Blood Brain Barrier (BBB). However, there is evidence which indicates that mice treated with SAM show increased levels of both SAM and SAM/SAH ratio in plasma and brain [29] and that peripherally administered SAM is effective in the treatment of several neuropsychiatric and neurological disorders, with chronic parenteral and oral administration of SAM resulting in increased CNS levels [53]. These evidences strongly indicate that this molecule can readily reach the brain parenchyma, suggesting it penetrates the continuous layer of brain endothelial cells lining the brain microvasculature constituting the BBB.…”

Section: Sam and The Blood Brain Barriermentioning

confidence: 99%

“…For these reasons, nutritional supplements restoring one-carbon metabolism alterations could restore physiological gene expression and oxidative buffering capacity, driving biochemical reactions to prevent or ameliorate degenerative processes. SAM diet supplementation has shown neuroprotective effects in mouse models of age-related diseases as well in clinical studies [28][29]61]. Due to the involvement of methyl nutrients metabolism in brain diseases, the role of SAM in neurodegeneration may be derived mainly from its methylating properties [27-29, 47, 97-98], however an important role in modulating antioxidant response in case of oxidative stress injury is recently emerged, being SAM a metabolically pleiotropic molecule participating and modulating diverse cellular processes.…”

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%

“…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][7][8][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 showing the role of SAM supplementation in restoring one-carbon metabolism alterations, particularly in neurodegenerative diseases [25][26][27][28][29]. SAM is currently marketed as a nutritional supplement worldwide, whereas it is sold as a prescription drug in several countries of the European Union.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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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Role of Post‐translational Modifications in Alzheimer's Disease

2020

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The global burden of Alzheimer's disease (AD) is growing. Valiant efforts to develop clinical candidates for treatment have continuously met with failure. Currently available palliative treatments are temporary and there is a constant need to search for reliable disease pathways, biomarkers and drug targets for developing diagnostic and therapeutic tools to address the unmet medical needs of AD. Challenges in drug‐discovery efforts raise further questions about the strategies of current conventional diagnosis; drug design; and understanding of disease pathways, biomarkers and targets. In this context, post‐translational modifications (PTMs) regulate protein trafficking, function and degradation, and their in‐depth study plays a significant role in the identification of novel biomarkers and drug targets. Aberrant PTMs of disease‐relevant proteins could trigger pathological pathways, leading to disease progression. Advancements in proteomics enable the generation of patterns or signatures of such modifications, and thus, provide a versatile platform to develop biomarkers based on PTMs. In addition, understanding and targeting the aberrant PTMs of various proteins provide viable avenues for addressing AD drug‐discovery challenges. This review highlights numerous PTMs of proteins relevant to AD and provides an overview of their adverse effects on the protein structure, function and aggregation propensity that contribute to the disease pathology. A critical discussion offers suggestions of methods to develop PTM signatures and interfere with aberrant PTMs to develop viable diagnostic and therapeutic interventions in AD.

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S-adenosylmethionine reduces the progress of the Alzheimer-like features induced by B-vitamin deficiency in mice

Cited by 115 publications

References 60 publications

Alzheimer’s Disease: Adult-Onset of Inborn Error of Methionine Metabolism

Alzheimer’s Disease: Adult-Onset of Inborn Error of Methionine Metabolism

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

Role of Post‐translational Modifications in Alzheimer's Disease

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