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Antioxidants (Basel). 2017 Sep 30;6(4). doi: 10.3390/antiox6040076.

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

Antioxidants (Basel, Switzerland)

Rosaria A Cavallaro, Vincenzina Nicolia, Maria Teresa Fiorenza, Sigfrido Scarpa, Andrea Fuso

Affiliations

  1. Department of Surgery "P. Valdoni", Sapienza University of Rome, Via A. Scarpa 14, 00161 Rome, Italy. [email protected].
  2. Department of Surgery "P. Valdoni", Sapienza University of Rome, Via A. Scarpa 14, 00161 Rome, Italy. [email protected].
  3. Division of Neuroscience, Department of Psychology, Sapienza University of Rome, Via dei Marsi 78, 00183 Rome, Italy. [email protected].
  4. IRCCS Santa Lucia Foundation, Via del Fosso di Fiorano 64-65, 00143 Rome, Italy. [email protected].
  5. Department of Surgery "P. Valdoni", Sapienza University of Rome, Via A. Scarpa 14, 00161 Rome, Italy. [email protected].
  6. Department of Surgery "P. Valdoni", Sapienza University of Rome, Via A. Scarpa 14, 00161 Rome, Italy. [email protected].
  7. Division of Neuroscience, Department of Psychology, Sapienza University of Rome, Via dei Marsi 78, 00183 Rome, Italy. [email protected].

PMID: 28973985 PMCID: PMC5745486 DOI: 10.3390/antiox6040076

Abstract

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.

Keywords: Alzheimer’s disease; S-adenosylmethionine; one-carbon metabolism; oxidative stress; superoxide dismutase

Conflict of interest statement

Sigfrido Scarpa and Andrea Fuso are co-owners of a patent (US 2011/0020301 A1) on SAM and SOD supplementation for treatment of Alzheimer’s Disease.

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