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Drawing of nerves with electrical impulses

Nerve health impacts how we think and how we move, but replenishing NAD in nerve cells is peculiarly difficult because the metabolic pathway used by niacin is not active in neurons. And yet degenerative nerve disorders and dementia are when we most might most need to maintain our NAD levels.


Here are the studies:

Aug 28, 2023

Brain - Neurons - Neurodegeneration - Ataxia

Expert Opinion on Investigational Drugs

Ataxia-telangiectasia clinical trial landscape and the obstacles to overcome

Kuhn, Katrina


Pharmacologic treatments that target oxidative stress, inflammation, and mitochondrial exhaustion may provide neurologic benefit in ataxia-telangiectasia.

Aug 25, 2023

Vision - Glaucoma - Neurons - Neurodegeneration

Current Issues in Molecular Biology

Axonal Protection by Oral Nicotinamide Riboside Treatment with Upregulated AMPK Phosphorylation in a Rat Glaucomatous Degeneration Model

Arizono, Ibuki


The present study revealed that oral NR administration (1000 mg/kg daily) exerted substantial axonal protection in ocular hypertension optic nerve damage. We also found apparent protective effects on retinal nerve fibers in this model... to our knowledge, this is the first study demonstrating axonal protection of NR against glaucomatous damage in both the optic nerve and retina...Since axonal degeneration precedes RGC body death in glaucoma, oral NR administration may help to inhibit further axonal degeneration, thereby preventing additional RGC death.

Aug 17, 2023

Neurons - Inflammation

Frontiers in Cellular Neuroscience

Nicotinamide enhances myelin production after demyelination through reduction of astrogliosis and microgliosis

Kaplanis, Stefanos loannis


Overall, we show that the increased myelin production that follows NAM treatment in vivo is accompanied by a decrease in both astrocyte and microglia accumulation at the lesion site. Our data indicate that NAM influences astrocytes and microglia directly, in favor of the remyelination process by promoting a less inflammatory environment.

Aug 6, 2023

Brain - Neurons - Neurodegeneration - Parkinsons

International Journal of Molecular Sciences

Exploring Molecular Targets for Mitochondrial Therapies in Neurodegenerative Diseases

Plascencia-Villa, German


Nicotinamide a different form of vitamin B3, which in the brain promotes the formation of NAD+, which usually declines with aging and neurodegeneration. A phase I clinical trial studied the effects of nicotinamide riboside (NR) oral intake (1000 mg for 30 days) in individuals with PD ( NCT03816020). Overall, NR treatment was well tolerated, promoting increased NAD levels in the brain (MRI scan and CSF) and increased brain glucose metabolism . The clinical benefits were associated with increased NAD levels and increased mitochondrial activity. This study advanced to phase II where the PD patients will take NR for up to 1 year; the results of this study are expected in 2024.

Aug 1, 2023

Brain - Neurons - Neurodegeneration - Parkinsons

Parkinsonism & Related Disorders

Nicotinamide riboside alleviates Parkinson's disease symptoms but downregulates dopamine metabolism

Turconi, Giorgio


We found that NR eased symptoms of disease by activating the mitochondrial unfolded protein response (UPRmt) via the transcription factor atfs-1. Similarly, in a proteasome inhibitor, lactacystin, -induced mouse model of PD, NR rescued mitochondrial dysfunction and behavioural deficits caused by lactacystin lesion. However, long-term NR supplementation, in conjunction with proteasome inhibition, resulted in decreased DA levels in both the lesioned and unlesioned sides of the substantia nigra with concomitant downregulation of key genes in DA metabolism. Our results suggest specific endpoints that should be monitored in ongoing NR clinical trials.

Jul 9, 2023

Diabetes - Inflammation - Neurons


Nicotinamide Prevents Diabetic Brain Inflammation via NAD+-Dependent Deacetylation Mechanisms

Torres-Méndez, Jeimy Katherine


NAM supplementation prevented brain inflammation and microglial activation inthe brains of diabetic mice.

Jul 2, 2023

Mitochondria - Neurons - Alpers


The NAD+ Precursor Nicotinamide Riboside Rescues Mitochondrial Defects and Neuronal Loss in iPSC derived Cortical Organoid of Alpers’ Disease

Hong, Yu


In this study, the role of NAD+ supplementation, specifically the administration of NR, was investigated as a potential therapeutic strategy to alleviate the pathological changes in Alpers’ syndrome...we provide evidence that NAD+ supplementation, specifically through NR therapy, could present a promising clinical avenue for neuroprotection not only in Alpers’ disease, but also in a broader spectrum of mitochondrial disorders.

Jun 23, 2023

Neurons - Neurodegneration - Alzheimer's


Effect of Exercise and Oral Niacinamide Mononucleotide on Improving Mitochondrial Autophagy in Alzheimer’s Disease

Wu, Weijia


This review summarizes recent studies on the effect of oral NMN on the enhancement of NAD+ in vivo and the improvements in mitochondrial autophagy abnormalities in AD through aerobic exercise, focusing on (1) how oral NMN improves the internal NAD+ level; (2) how exercise regulates the content of NAD+ in the body; (3) the relationship between exercise activation of NAD+ and AMPK; (4) how SIRT1 is regulated by NAD+ and AMPK and activates PGC-1α to mediate mitochondrial autophagy through changes in mitochondrial dynamics. By summarizing the results of the above four aspects, and combined with the synthesis of NAD+ in vivo, we can infer how exercise elevates the level of NAD+ in vivo to mediate mitochondrial autophagy, so as to propose a new hypothesis that exercise interferes with Alzheimer’s disease (AD).

May 4, 2023

Neurons - Autism - Social Behavior

Frontiers in Immunology

Remission of social behavior impairment by oral administration of a precursor of NAD in CD157, but not in CD38, knockout mice

Gerasimenko, Maria


Nicotinamide riboside is beneficial for treating social impairments in young and aged people, some of which are based on impairments of oxytocin and/or oxytocin release;...CD157KO and CD38KO mice displayed no social preference (that is, more interest towards a novel mouse than a familiar one) behavior. This defect was rescued after oral gavage administration of nicotinamide riboside for 12 days in CD157KO mice, but not in CD38KO mice. Social memory was not observed in CD157KO and CD38KO mice...Nicotinamide riboside is less harmful and has beneficial effect on defects in recovery from social behavioral, for which CD38 is required in mice.

Apr 26, 2023

Neurons - Charcot-Marie-Tooth - Peripheral Neuropathy


Therapeutic Potential of Vitamins in Charcot-Marie-Tooth Disease with the Compromised Status of the Vitamin-Dependent Processes

Bunik, Victoria


The decreased NAD+ levels in the blood of CMT patients, compared to healthy subjects, suggest that the patients may benefit from the administration of NAD+ precursors. The NAD+ biosynthetic intermediates, such as nicotinamide riboside, may decelerate the progression of CMT disease with age.

Mar 15, 2023

Diabetes - GI Tract ⎼ Neurons

Digestive Diseases and Sciences

Nicotinamide Riboside Improves Enteric Neuropathy in Streptozocin-Induced Diabetic Rats Through Myenteric Plexus Neuroprotection

Costa, Christopher


NR treatment led to functional improvement in total gastrointestinal transit time in induced diabetic animals. This was associated with neuroprotection in the myenteric plexuses of both small and large intestines of induced diabetic rats. This represents an important first step in showing NR’s benefit as a treatment for diabetic enteric neuropathy.

Feb 6, 2023

Neurons - Brain - Parkinson's

Brain Sciences

Could Vitamins Have a Positive Impact on the Treatment of Parkinson’s Disease?



"...Vitamin B3 supplementation has been shown to alleviate various symptoms associated with PD...Mechanistically, vitamin B3 promotes the biosynthesis of the classical enzyme cofactor nicotinamide adenine dinucleotide (NAD) and mediates the release of nicotinamide by poly-ADP ribosylation. This generates an anti-inflammatory response, which alleviates DA-ergic neurodegeneration caused by neuroinflammation. These findings suggest that dietary supplementation with vitamin B3 may ameliorates oxidative stress and neuroinflammation, which would therefore prevent the death of DA-ergic neurons..."

Jan 19, 2023

Neurons - Spinal Cord Injury


Elevation of NAD+ by nicotinamide riboside spares spinal cord tissue from injury and promotes locomotor recovery

Metcalfe, Mariajose


Administration of the NAD+ precursor, NR, to elevate NAD+ within the injured spinal cord mitigates the tissue damage and functional decline that occurs following spinal cord injury….administration of NR enhances NAD+ levels within the injured rat spinal cord, reduces tissue damage, and improves locomotor recovery after a thoracic spinal cord contusion injury in rats. Collectively, the results show that NR is a safe and effective bioavailable agent that can mitigate spinal cord damage.

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.

Dec 26, 2022

Neurons - Neurodegeneration - Alzheimer's Disease - Parkinson's Disease

Life Sciences

Combined metabolic activators improve metabolic functions in the animal models of neurodegenerative diseases

Turkez, Hasan


We showed that combined metabolic activators [including nicotinamide riboside] administration significantly improved behavioural scores in parallel with the neurohistological outcomes in the Alzheimer's Disease and Parkinson's Disease animal models and is a promising treatment for improving the metabolic parameters and brain functions in neurodegenerative diseases.

Dec 14, 2022

Brain - Neurons - Neurodegeneration - Inflammation - Alzheimer's

Aging Cell

Oral nicotinamide riboside raises NAD+ and lowers biomarkers of neurodegenerative pathology in plasma extracellular vesicles enriched for neuronal origin

Vreones, Michael


We report the first study examining [extracellular vesicles enriched for neuronal origin or "NEV"] NEV biomarkers in response to oral NR supplementation. Our primary analysis of NAD+ and NADH in NEVs suggests an increase in neuronal NAD+ concentration in response to oral NR supplementation....We demonstrate that oral NR supplementation [in humans] increases NAD+ levels in NEVs ...These findings support the ability of orally administered NR to augment neuronal NAD+ levels and modify biomarkers related to neurodegenerative pathology in humans.

Aug 30, 2022

Neurons - Leigh Syndrome

Clinical and Translational Discovery

How to mitigate neurological and cardiac decompensation in Leigh syndrome: Can nicotinamide riboside be an answer?

Prigione, Allesandro


Leigh syndrome is the most common form of mitochondrial disease in children. The mechanisms underlying its pathogenesis are not fully understood and no therapies are approved for the treatment of patients with LS. In a new study, Yoon and colleagues1 shed light on the pathophysiological mechanisms of cardio-encephalomyopathy in LS and demonstrates that nicotiname riboside (NR) provides significant amelioration in disease models of LS

Jul 25, 2022

Neurons - Leigh Syndrome - Mitochondrial Dysfunction

Clinical and Translational Medicine

Metabolic rescue ameliorates mitochondrial encephalo-cardiomyopathy in murine and human iPSC models of Leigh syndrome

Yoon, Jin-Young


Our study reveals direct mechanistic explanations of the observed cardiac bradyarrhythmia, diastolic dysfunction and neuronal apoptosis in mouse and human induced pluripotent stem cells (iPSC) models of Leigh Syndrome….Metabolic rescue by nicotinamide riboside (NR) supplementation increased intracellular NAD+/ NADH, restored metabolic derangement, reversed protein hyperacetylation through NAD+‐dependent Sirtuin deacetylase, and ameliorated cardiomyopathic phenotypes...NR also attenuated neuronal apoptosis and microglial activation...

Jun 27, 2022

Neurons - Neuropathy - Cancer - Chemotherapy

Neuro-Oncology Advances

Nicotinamide riboside alleviates cisplatin-induced peripheral neuropathy via SIRT2 activation

Acklin, Scarlett


We show that NR, an NAD+ precursor and pharmacologic activator of SIRT2, effectively prevents and alleviates CIPN in mice. We present in vitro and in vivo genetic evidence to illustrate the specific dependence on SIRT2 of NR-mediated CIPN mitigation. Importantly, we demonstrate that NAD+ mediates SIRT2-dependent neuroprotection without inhibiting cisplatin cytotoxic activity against cancer cells. NAD+ may, in fact, further sensitize certain cancer cell types to cisplatin.

Apr 28, 2022

Diabetes - Neuropathy - Neurons

International Journal of Molecular Sciences

NAD+ Precursors Repair Mitochondrial Function in Diabetes and Prevent Experimental Diabetic Neuropathy

Chandrasekaran, Krish


Diabetic peripheral neuropathy (DPN) is a common neurological complication of diabetes. Currently, there is no therapy that permanently prevents or reverses neuropathy. ...Correction of NAD+ depletion [with dietary NR] in dorsal root ganglion neurons may be sufficient to prevent diabetic peripheral neuropathy, but does not significantly affect glucose tolerance, insulin levels, or insulin resistance.

NAD Research - Nerves / Neurons

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