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Abstract Title:

Nicotinamide Riboside and Pterostilbene Cooperatively Delay Motor Neuron Failure in ALS SOD1Mice.

Abstract Source:

Mol Neurobiol. 2020 Nov 10. Epub 2020 Nov 10. PMID: 33174130

Abstract Author(s):

Elena Obrador, Rosario Salvador, Patricia Marchio, Rafael López-Blanch, Ali Jihad-Jebbar, Pilar Rivera, Soraya L Vallés, Salvador Banacloche, Javier Alcácer, Nuria Colomer, Javier A Coronado, Sandra Alandes, Eraci Drehmer, María Benlloch, José M Estrela

Article Affiliation:

Elena Obrador

Abstract:

Oxidative stress-induced damage is a major mechanism in the pathophysiology of amyotrophic lateral sclerosis (ALS). A recent human clinical trial showed that the combination of nicotinamide riboside (NR) and pterostilbene (PT), molecules with potential to interfere in that mechanism, was efficacious in ALS patients. We examined the effect of these molecules in SOD1transgenic mice, a well-stablished model of ALS. Assessment of neuromotor activity and coordination was correlated with histopathology, and measurement of proinflammatory cytokines in the cerebrospinal fluid. Cell death, Nrf2- and redox-dependent enzymes and metabolites, and sirtuin activities were studied in isolated motor neurons. NR and PT increased survival and ameliorated ALS-associated loss of neuromotor functions in SOD1transgenic mice. NR and PT also decreased the microgliosis and astrogliosis associated with ALS progression. Increased levels of proinflammatory cytokines were observed in the cerebrospinal fluid of mice and humans with ALS. NR and PT ameliorated TNFα-induced oxidative stress and motor neuron death in vitro. Our results support the involvement of oxidative stress, specific Nrf2-dependent antioxidant defenses, and sirtuins in the pathophysiology of ALS. NR and PT interfere with the mechanisms leading to the release of proapoptotic molecular signals by mitochondria, and also promote mitophagy.

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