Nicotinamide Riboside and Pterostilbene Cooperatively Delay Motor Neuron Failure in ALS SOD1 G93A Mice.

Autor: Obrador E; Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, 15 Av. Blasco Ibañez, 46010, Valencia, Spain., Salvador R; Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, 15 Av. Blasco Ibañez, 46010, Valencia, Spain., Marchio P; Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, 15 Av. Blasco Ibañez, 46010, Valencia, Spain., López-Blanch R; Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, 15 Av. Blasco Ibañez, 46010, Valencia, Spain., Jihad-Jebbar A; Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, 15 Av. Blasco Ibañez, 46010, Valencia, Spain., Rivera P; Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, 15 Av. Blasco Ibañez, 46010, Valencia, Spain., Vallés SL; Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, 15 Av. Blasco Ibañez, 46010, Valencia, Spain., Banacloche S; Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, 15 Av. Blasco Ibañez, 46010, Valencia, Spain., Alcácer J; Pathology Laboratory, Quirón Hospital, 46010, Valencia, Spain., Colomer N; Pathology Laboratory, Quirón Hospital, 46010, Valencia, Spain., Coronado JA; Pathology Laboratory, Quirón Hospital, 46010, Valencia, Spain., Alandes S; Pathology Laboratory, Quirón Hospital, 46010, Valencia, Spain., Drehmer E; Department of Health and Functional Valorization, Catholic University of San Vicente Martir, 46001, Valencia, Spain., Benlloch M; Department of Health and Functional Valorization, Catholic University of San Vicente Martir, 46001, Valencia, Spain., Estrela JM; Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, 15 Av. Blasco Ibañez, 46010, Valencia, Spain. jose.m.estrela@uv.es.
Jazyk: angličtina
Zdroj: Molecular neurobiology [Mol Neurobiol] 2021 Apr; Vol. 58 (4), pp. 1345-1371. Date of Electronic Publication: 2020 Nov 10.
DOI: 10.1007/s12035-020-02188-7
Abstrakt: 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 SOD1 G93A transgenic 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 SOD1 G93A transgenic 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.
Databáze: MEDLINE
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