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Diagram showing neurodegeneration in ALS - Amyotrophic Lateral Sclerosis - 1200x700

NAD deficits seem to play some role in a number of neurodegenerative diseases, including ALS:


Here are the studies:

Jan 13, 2023

Neurons - Neurodegeneration - Parkinsons - Alzheimer's - Huntington's Disease - ALS

International Journal of Molecular Sciences

A Promising Strategy to Treat Neurodegenerative Diseases by SIRT3 Activation

Tyagi, Alpna


NMN and NR can be expected to have broad-spectrum effects in the treatment of neurodegenerative diseases by activating these sirtuins.

Oct 20, 2022

Brain - Neurodegeneration - Mitochondria - Parkinsons - Alzheimers - ALS

International Journal of Molecular Sciences

Mitochondrial Dysfunction and Neurodegenerative Disorders: Role of Nutritional Supplementation

Mantle, David


We have selected a number of neurodegenerative disorders that are known to involve mitochondrial dysfunction in their pathogenesis. We have further selected a number of nutrients that have a key role in mitochondrial function. We then correlated data on the deficiency (Table 1) and supplementation of these nutrients (Table 2) in the said neurodegenerative disorders. In this review, we have therefore provided a rationale for a combination of CoQ10, B-vitamins/NADH, l-carnitine, vitamin D, and alpha-lipoic acid to support the future treatment of these neurodegenerative disorders.

Nov 10, 2020

Brain - ALS - Neurons

Molecular Neurobiology

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

Obrador, Elena


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 SOD1G93A 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 SOD1G93A 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.

May 1, 2020

Brain - ALS - Neurons

Experimental Neurology

Evaluation of the NAD(+) biosynthetic pathway in ALS patients and effect of modulating NAD(+) levels in hSOD1-linked ALS mouse models.

Harlan, Benjamin A.


Amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of motor neurons. Astrocytes from diverse ALS models induce motor neuron death in co-culture. Enhancing NAD+ availability, or increasing the expression of the NAD+-dependent deacylases SIRT3 and SIRT6, abrogates their neurotoxicity in cell culture models. To determine the effect of increasing NAD+ availability in ALS mouse models we used two strategies, ablation of a NAD+-consuming enzyme (CD38) and supplementation with a bioavailable NAD+ precursor (nicotinamide riboside, NR). Deletion of CD38 had no effect in the survival of two hSOD1-linked ALS mouse models. On the other hand, NR-supplementation delayed motor neuron degeneration, decreased markers of neuroinflammation in the spinal cord, appeared to modify muscle metabolism and modestly increased the survival of hSOD1G93A mice. In addition, we found altered expression of enzymes involved in NAD+ synthesis (NAMPT and NMNAT2) and decreased SIRT6 expression in the spinal cord of ALS patients, suggesting deficits of this neuroprotective pathway in the human pathology. Our data denotes the therapeutic potential of increasing NAD+ levels in ALS. Moreover, the results indicate that the approach used to enhance NAD+ levels critically defines the biological outcome in ALS models, suggesting that boosting NAD+ levels with the use of bioavailable precursors would be the preferred therapeutic strategy for ALS.

Jan 1, 2020

Brain - ALS - Neurons

International Journal of Biological Sciences

Nicotinamide Riboside Enhances Mitochondrial Proteostasis and Adult Neurogenesis through Activation of Mitochondrial Unfolded Protein Response Signaling in the Brain of ALS SOD1G93A Mice

Zhou, Qui


...Regulatory mechanisms and functions of NAD+ metabolism in ALS are still unknown. Thus, we hypothesized the aggregation of human SOD1 toxic protein and the fate of NSCs/NPCs in the ALS disease could be improved by the administration of nicotinamide riboside (NR), an NAD+ precursor...In summary, these findings reveal that the administration of NR activates UPRmt signaling, modulates mitochondrial proteostasis and improves the adult neurogenesis in the brain of SOD1G93A mice.

Oct 1, 2019

Brain - Aging - Neurons - Alzheimer's - Parkinson's - Huntington's - ALS

Cell Metabolism

NAD+ in Brain Aging and Neurodegenerative Disorders

Lautrup, Sofie


NAD+ is a pivotal metabolite involved in cellular bioenergetics, genomic stability, mitochondrial homeostasis, adaptive stress responses, and cell survival. Multiple NAD+-dependent enzymes are involved in synaptic plasticity and neuronal stress resistance. Here, we review emerging findings that reveal key roles for NAD+ and related metabolites in the adaptation of neurons to a wide range of physiological stressors and in counteracting processes in neurodegenerative diseases, such as those occurring in Alzheimer’s, Parkinson’s, and Huntington diseases, and amyotrophic lateral sclerosis. Advances in understanding the molecular and cellular mechanisms of NAD+-based neuronal resilience will lead to novel approaches for facilitating healthy brain aging and for the treatment of a range of neurological disorders.

NAD Research - ALS

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