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S-Adenosylmethionine and Superoxide Dismutase 1 Synergistically Counteract Alzheimer’s Disease Features Progression in TgCRND8 Mice

Recent evidence emphasizes the role of dysregulated one-carbon metabolism in Alzheimer’s Disease (AD). Exploiting a nutritional B-vitamin deficiency paradigm, we have previously shown that PSEN1 and BACE1 activity is modulated by one-carbon metabolism, leading to increased amyloid production. We hav...

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Autores principales: Cavallaro, Rosaria A., Nicolia, Vincenzina, Fiorenza, Maria Teresa, Scarpa, Sigfrido, Fuso, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745486/
https://www.ncbi.nlm.nih.gov/pubmed/28973985
http://dx.doi.org/10.3390/antiox6040076
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author Cavallaro, Rosaria A.
Nicolia, Vincenzina
Fiorenza, Maria Teresa
Scarpa, Sigfrido
Fuso, Andrea
author_facet Cavallaro, Rosaria A.
Nicolia, Vincenzina
Fiorenza, Maria Teresa
Scarpa, Sigfrido
Fuso, Andrea
author_sort Cavallaro, Rosaria A.
collection PubMed
description Recent evidence emphasizes the role of dysregulated one-carbon metabolism in Alzheimer’s Disease (AD). Exploiting a nutritional B-vitamin deficiency paradigm, we have previously shown that PSEN1 and BACE1 activity is modulated by one-carbon metabolism, leading to increased amyloid production. We have also demonstrated that S-adenosylmethionine (SAM) supplementation contrasted the AD-like features, induced by B-vitamin deficiency. In the present study, we expanded these observations by investigating the effects of SAM and SOD (Superoxide dismutase) association. TgCRND8 AD mice were fed either with a control or B-vitamin deficient diet, with or without oral supplementation of SAM + SOD. We measured oxidative stress by lipid peroxidation assay, PSEN1 and BACE1 expression by Real-Time Polymerase Chain Reaction (PCR), amyloid deposition by ELISA assays and immunohistochemistry. We found that SAM + SOD supplementation prevents the exacerbation of AD-like features induced by B vitamin deficiency, showing synergistic effects compared to either SAM or SOD alone. SAM + SOD supplementation also contrasts the amyloid deposition typically observed in TgCRND8 mice. Although the mechanisms underlying the beneficial effect of exogenous SOD remain to be elucidated, our findings identify that the combination of SAM + SOD could be carefully considered as co-adjuvant of current AD therapies.
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spelling pubmed-57454862018-01-02 S-Adenosylmethionine and Superoxide Dismutase 1 Synergistically Counteract Alzheimer’s Disease Features Progression in TgCRND8 Mice Cavallaro, Rosaria A. Nicolia, Vincenzina Fiorenza, Maria Teresa Scarpa, Sigfrido Fuso, Andrea Antioxidants (Basel) Article Recent evidence emphasizes the role of dysregulated one-carbon metabolism in Alzheimer’s Disease (AD). Exploiting a nutritional B-vitamin deficiency paradigm, we have previously shown that PSEN1 and BACE1 activity is modulated by one-carbon metabolism, leading to increased amyloid production. We have also demonstrated that S-adenosylmethionine (SAM) supplementation contrasted the AD-like features, induced by B-vitamin deficiency. In the present study, we expanded these observations by investigating the effects of SAM and SOD (Superoxide dismutase) association. TgCRND8 AD mice were fed either with a control or B-vitamin deficient diet, with or without oral supplementation of SAM + SOD. We measured oxidative stress by lipid peroxidation assay, PSEN1 and BACE1 expression by Real-Time Polymerase Chain Reaction (PCR), amyloid deposition by ELISA assays and immunohistochemistry. We found that SAM + SOD supplementation prevents the exacerbation of AD-like features induced by B vitamin deficiency, showing synergistic effects compared to either SAM or SOD alone. SAM + SOD supplementation also contrasts the amyloid deposition typically observed in TgCRND8 mice. Although the mechanisms underlying the beneficial effect of exogenous SOD remain to be elucidated, our findings identify that the combination of SAM + SOD could be carefully considered as co-adjuvant of current AD therapies. MDPI 2017-09-30 /pmc/articles/PMC5745486/ /pubmed/28973985 http://dx.doi.org/10.3390/antiox6040076 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cavallaro, Rosaria A.
Nicolia, Vincenzina
Fiorenza, Maria Teresa
Scarpa, Sigfrido
Fuso, Andrea
S-Adenosylmethionine and Superoxide Dismutase 1 Synergistically Counteract Alzheimer’s Disease Features Progression in TgCRND8 Mice
title S-Adenosylmethionine and Superoxide Dismutase 1 Synergistically Counteract Alzheimer’s Disease Features Progression in TgCRND8 Mice
title_full S-Adenosylmethionine and Superoxide Dismutase 1 Synergistically Counteract Alzheimer’s Disease Features Progression in TgCRND8 Mice
title_fullStr S-Adenosylmethionine and Superoxide Dismutase 1 Synergistically Counteract Alzheimer’s Disease Features Progression in TgCRND8 Mice
title_full_unstemmed S-Adenosylmethionine and Superoxide Dismutase 1 Synergistically Counteract Alzheimer’s Disease Features Progression in TgCRND8 Mice
title_short S-Adenosylmethionine and Superoxide Dismutase 1 Synergistically Counteract Alzheimer’s Disease Features Progression in TgCRND8 Mice
title_sort s-adenosylmethionine and superoxide dismutase 1 synergistically counteract alzheimer’s disease features progression in tgcrnd8 mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745486/
https://www.ncbi.nlm.nih.gov/pubmed/28973985
http://dx.doi.org/10.3390/antiox6040076
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