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.

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. - In: ANTIOXIDANTS. - ISSN 2076-3921. - STAMPA. - 6:4(2017), pp. 1-17. [10.3390/antiox6040076]

S-adenosylmethionine and superoxide dismutase 1 synergistically counteract Alzheimer's disease features progression in tgCRND8 mice

Cavallaro, Rosaria A
Writing – Original Draft Preparation
;
Nicolia, Vincenzina
Investigation
;
Fiorenza, Maria Teresa
Writing – Original Draft Preparation
;
Scarpa, Sigfrido
Writing – Original Draft Preparation
;
Fuso, Andrea
2017

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.
2017
Alzheimer’s disease; S-adenosylmethionine; one-carbon metabolism; oxidative stress; superoxide dismutase
01 Pubblicazione su rivista::01a Articolo in rivista
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. - In: ANTIOXIDANTS. - ISSN 2076-3921. - STAMPA. - 6:4(2017), pp. 1-17. [10.3390/antiox6040076]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1019783
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