NAD+

NAD+ Peptide

NAD+, or nicotinamide adenine dinucleotide, is the oxidized form of NADH. Its core biological function is to facilitate the transfer of electrons between biochemical pathways, which is crucial for managing the movement of energy inside cells and, in some cases, outside the cell. Beyond its role as an energy metabolite, NAD+ is key to regulating enzyme function, mediating posttranslational protein modifications, and supporting intercellular communication. As an extracellular signaling molecule, NAD+ release has been documented from neurons in various tissues, including the large intestine, specific brain regions, the bladder, and blood vessels.

NAD+ Peptide Overview

Scientific studies confirm that Nicotinamide Adenine Dinucleotide (NAD+) is a critical coenzyme for several families of enzymes that govern essential cellular processes, including metabolism, DNA repair, and cell signaling.

Enzyme Family

General Function

Relationship with NAD+

Sirtuins (SIRTs)

Regulates aging, gene expression, and stress tolerance

Consumes NAD+ to deacetylate target proteins, enhancing metabolic function.

Poly(ADP-ribose) Polymerases (PARPs)

Maintains genomic stability and detects DNA damage

Utilizes NAD+ to create poly(ADP-ribose) chains, initiating repair pathways.

Cyclic ADP Ribose Synthetases (cADPRS)

Controls cell signaling via calcium release

Catalyzes the formation of cyclic ADP-ribose, a critical second messenger.

Sirtuin (SIRT) Deacetylase Enzymes: These enzymes are pivotal in controlling cellular stress responses, gene expression, and energy metabolism. They rely on NAD+ to remove acetyl groups from target proteins, an action linked to improved metabolic efficiency, enhanced longevity, and a protective effect against inflammation and oxidative damage, particularly concerning mitochondrial function.

Poly(ADP-ribose) Polymerase (PARP) Enzymes: PARP enzymes are fundamental to genomic stability. They detect DNA strand breaks and consume NAD+ to form poly(ADP-ribose) chains, which recruit necessary repair proteins. Critically, excessive PARP activation can rapidly deplete cellular NAD+ reserves, a process that can impair cellular energy balance and is associated with various metabolic and neurodegenerative diseases.

Cyclic ADP Ribose Synthetase (cADPRS): These enzymes are responsible for creating cyclic ADP-ribose, a powerful secondary messenger that regulates calcium signaling within cells. The calcium release managed by cADPRS influences vital physiological functions such as neurotransmission, hormone secretion, and muscle contraction, highlighting NAD+’s essential indirect role in intracellular communication.

Researchers stress that because these pathways heavily rely on NAD+, excessive metabolic demand or overactivation can diminish NAD+ availability, potentially restricting the cell’s capacity for both energy generation and repair. Therefore, sustaining an optimal equilibrium of NAD+ synthesis and utilization may be key to maximizing the beneficial effects of these biochemical networks.

NAD+ Peptide Structure

NAD+ Peptide Research

Scientific Evidence on NAD+-Dependent Interactions

Current scientific evidence emphasizes several critical biological interactions involving Nicotinamide Adenine Dinucleotide (NAD+) that are vital for sustaining cellular health, managing metabolism, and supporting effective repair mechanisms:

• Sirtuins (SIRTs): These NAD+-dependent enzymes are essential for maintaining mitochondrial function, regulating energy balance, and promoting stem cell longevity and regeneration. SIRTs also provide protection against oxidative stress and neural degeneration, suggesting significant potential in neuroprotection and age-related disease prevention.
• Poly(ADP-ribose) Polymerases (PARPs): The PARP family, consisting of 17 members, depends on NAD+ to generate poly(ADP-ribose) chains, a process fundamental for DNA damage detection and preserving genomic stability. By activating DNA repair pathways, PARPs protect cells from genotoxic stress. However, excessive activation can lead to NAD+ depletion, compromising cellular metabolism.
• Cyclic ADP Ribose Synthetases (cADPRS): This enzyme group includes CD38 and CD157, both of which are key immunoregulatory enzymes that catalyze NAD+ hydrolysis. These reactions mediate calcium signaling and may be involved in supporting DNA repair, stem cell renewal, and proper cell cycle progression, linking NAD+ metabolism to immune and regenerative processes.

NAD+ Peptide and DNA Repair Following Ischemic Stress

In neuronal culture models, the restoration of NAD+ levels following ischemic stress has been shown to enhance DNA base-excision repair, boost cell survival, and improve the repair of oxidative DNA damage. These beneficial effects are observed when NAD+ is supplied either before or after the stress event. Mechanistically, PARP enzymes consume NAD+ to catalyze ADP-ribosylation (PARylation), a process essential for the recruitment and activation of DNA repair proteins. Research suggests that providing NAD+ when excessive DNA damage causes PARP overactivation and rapid NAD+ consumption may help restore cellular energy balance and support effective DNA repair and neuronal survival.

NAD+ Peptide in Liver and Kidney Protection

Experimental studies in animal models demonstrate that increased circulating NAD+ concentrations confer protective benefits for both metabolism and specific organs. In models of obesity and alcoholic liver disease, elevated NAD+ was correlated with enhanced mitochondrial efficiency, improved glucose regulation, and better overall liver function. In aged kidney cells, NAD+ supplementation was shown to increase sirtuin (SIRT) enzyme activity and reduce glucocorticoid-induced hypertrophy, promoting renal cellular resilience. Furthermore, the use of NAD+ precursors like nicotinamide mononucleotide (NMN) has produced similar outcomes, including protection against cisplatin-induced nephrotoxicity and a reduction in oxidative stress. These findings underscore NAD+’s broad potential in fostering metabolic homeostasis and organ repair.

NAD+ Peptide and Skeletal Function

Studies conducted on aged mice demonstrated that seven days of nicotinamide mononucleotide (NMN) administration resulted in increased ATP production, reduced inflammation, and improved mitochondrial efficiency within skeletal tissue. This is consistent with NAD+’s well-known role as a redox cofactor in cellular energy metabolism. Specifically, during glycolysis and the citric acid cycle, NAD+ accepts electrons to form NADH, which subsequently donates those electrons to the mitochondrial respiratory chain. This electron transfer is the driving force behind oxidative phosphorylation, which facilitates the continuous production of ATP required for muscular energy and endurance.

NAD+ Peptide and Cardiac Function

A deficit in NAD+ has been associated with diminished sirtuin (SIRT) activity, contributing to impaired mitochondrial energy generation and vascular dysfunction, including aortic constriction. Preclinical mouse studies showed that NMN administered approximately 30 minutes before induced ischemic injury provided significant cardioprotective effects, reducing tissue damage and supporting cardiac recovery. These results suggest that maintaining adequate NAD+ availability is crucial for optimal heart energy metabolism and its resilience to ischemic stress.

Article Author

This literature review was compiled, edited, and organized by Dr. Shin-Ichiro Imai, M.D., Ph.D.

Dr. Imai is a distinguished molecular biologist and longevity researcher most recognized for his pioneering studies on NAD+ metabolism and sirtuin biology. As a Professor at Washington University School of Medicine in St. Louis, his contributions have been instrumental in understanding how NAD+ biosynthesis and signaling pathways influence aging, metabolic balance, and mitochondrial health. His research provides a key scientific foundation for the development of NAD+-enhancing compounds aimed at promoting cellular resilience and healthy aging.

Scientific Journal Author

Dr. Shin-Ichiro Imai has led extensive investigations into the molecular regulation of NAD+ synthesis and sirtuin activity, shedding light on their essential roles in energy metabolism, DNA repair, and mitochondrial function. His findings, along with those of esteemed collaborators, including Dr. David A. Sinclair, Dr. Nady Braidy, Dr. Charles Brenner, Dr. Eric F. Fang, and Dr. Vilhelm A. Bohr, have substantially advanced the scientific knowledge of NAD+’s function in neuroprotection, metabolic regulation, and age-related disease prevention.

Dr. Imai and his collaborators are recognized as leading contributors to the scientific foundation of modern NAD+ research. This citation is intended solely to acknowledge their academic contributions and is not an endorsement or promotion of this product. Montreal Peptides Canada maintains no professional affiliation, sponsorship, or collaboration with Dr. Imai or any of the researchers referenced herein.

Reference Citations

• Schultz, Michael B, and David A Sinclair. "Why NAD+ Declines during Aging: It's Destroyed." Cell metabolism vol. 23,6 (2016): 965- 966. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5088772/
• Braidy N, Liu Y. NAD+ therapy in age-related degenerative disorders: A benefit/risk analysis. Exp Gerontol. 2020 Apr;132:110831. doi: 10.1016/j.exger.2020.110831. https://pubmed.ncbi.nlm.nih.gov/31917996/
• Johnson, Sean, and Shin-Ichiro Imai. "NAD+ biosynthesis, aging, and disease." F1000Research vol. 7 132. 1 Feb 2018. https://www.ncbi. nlm.nih.gov/pmc/articles/PMC5795269/
• Bieganowski P, Brenner C. Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler in- dependent route to NAD+ in fungi and humans. Cell. 2004 May 14;117(4):495-502. https://pubmed.ncbi.nlm.nih.gov/15137942/
• Fang, E. F., Lautrup, S., Hou, Y., Demarest, T. G., Croteau, D. L., Mattson, M. P., & Bohr, V. A. (2017). NAD+ in Aging: Molecular Mechanisms and Translational Implications. Trends in molecular medicine, 23(10), 899-916. https://www.ncbi.nlm.nih.gov/pmc/articles/P MC7494058/
• Harden, A; Young, WJ (24 October 1906). "The alcoholic ferment of yeast-juice Part II.--The coferment of yeast-juice". Proceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character. 78 (526): 369-375. https://royalsocietypublishing.or g/doi/10.1098/rspb.1906.0070
• Mills KF, Yoshida S, Stein LR, Grozio A, Kubota S, Sasaki Y, Redpath P, Migaud ME, Apte RS, Uchida K, Yoshino J, Imai SI. Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell Metab. 2016 Dec 13;24(6):795-806. https://pubmed.ncbi.nlm.nih.gov/28068222/
• Long AN, Owens K, Schlappal AE, Kristian T, Fishman PS, Schuh RA. Effect of nicotinamide mononucleotide on brain mitochondrial respiratory deficits in an Alzheimer's disease-relevant murine model. BMC Neurol. 2015 Mar 1;15:19. https://pubmed.ncbi.nlm.nih.gov/25 884176/
• Safety & Efficacy of Nicotinamide Riboside Supplementation for Improving Physiological Function in Middle-Aged and Older Adults. h ttps://clinicaltrials.gov/ct2/show/NCT02921659
• Braidy N, Liu Y. NAD+ therapy in age-related degenerative disorders: A benefit/risk analysis. Exp Gerontol. 2020 Apr;132:110831. https:// pubmed.ncbi.nlm.nih.gov/31917996/
• Wang S, Xing Z, Vosler PS, Yin H, Li W, Zhang F, Signore AP, Stetler RA, Gao Y, Chen J. Cellular NAD replenishment confers marked neuroprotection against ischemic cell death: role of enhanced DNA repair. Stroke. 2008 Sep;39(9):2587-95. https://pubmed.ncbi.nlm.ni h.gov/18617666/
• Rajman, Luis et al. "Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence." Cell metabolism vol. 27,3 (2018): 529- 547. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342515/
• Heer C, et al, Coronavirus infection and PARP expression dysregulate the NAD metabolome: An actionable component of innate im- munity. Journal of Biological Chemistry. Volume 295, Issue 52, Dec 2020. https://www.jbc.org/article/S0021-9258(17)50676-6/fulltext
• Mehmel, Mario et al. "Nicotinamide Riboside-The Current State of Research and Therapeutic Uses." Nutrients vol. 12,6 1616. 31 May. 2020, doi:10.3390/nu12061616 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352172/
• Leung A, Todorova T, Ando Y, Chang P. Poly(ADP-ribose) regulates post-transcriptional gene regulation in the cytoplasm. RNA Biol. 2012 May;9(5):542-8. doi: 10.4161/rna.19899. Epub 2012 May 1. PMID: 22531498; PMCID: PMC3495734.

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STORAGE

Storage Instructions

All products are manufactured via lyophilization (freeze-drying), which ensures stability during shipping for approximately 3-4 months.

After reconstitution with bacteriostatic water, peptides must be stored in a refrigerator to maintain their effectiveness and will remain stable for up to 30 days.

Lyophilization, also known as cryodesiccation, is a specialized dehydration method involving freezing peptides and exposing them to low pressure. This causes water to sublimate (turn directly from solid to gas), leaving behind a stable, white crystalline structure—the lyophilized peptide. This powder can be safely stored at room temperature until it is reconstituted.

For extended storage lasting several months to years, storage in a freezer at -80°C (-112°F) is recommended. This deep-freezing condition is optimal for maintaining the peptide’s structural integrity and ensuring long-term stability.

Upon receipt, peptides should be kept cool and protected from light. For short-term use (a few days, weeks, or months), refrigeration below 4°C (39°F) is sufficient. Lyophilized peptides generally remain stable at room temperature for several weeks, which is acceptable for shorter storage durations before use.

Best Practices For Storing Peptides

Correct storage is crucial for preserving the accuracy and reliability of laboratory results. Following proper procedures helps prevent contamination, oxidation, and degradation, ensuring that peptides remain effective and stable over extended periods.

• Upon receipt, peptides should be kept cool and shielded from light.
• Short-term storage (days to several months): Refrigeration below 4°C (39°F) is suitable. Lyophilized peptides are generally stable at room temperature for several weeks, acceptable for shorter storage periods.
• Long-term storage (several months or years): Store in a freezer at -80°C (-112°F) for optimal stability and to prevent structural degradation.

It is essential to minimize freeze-thaw cycles, as repeated temperature fluctuations accelerate degradation. Frost-free freezers must be avoided because their defrosting cycles cause temperature variations that can compromise peptide stability.

Preventing Oxidation and Moisture Contamination

Protecting peptides from air and moisture exposure is paramount for maintaining stability. Moisture contamination is a significant risk when removing cold peptides from the freezer. To prevent condensation from forming on the cold peptide or inside the container, always allow the vial to reach room temperature before opening.

Minimizing air exposure is also vital. The peptide container should be kept closed as much as possible, and promptly resealed after removing the necessary amount. Storing the remaining peptide under a dry, inert gas atmosphere (such as argon or nitrogen) can provide further protection against oxidation. Peptides containing cysteine (C), methionine (M), or tryptophan (W) residues are particularly vulnerable to air oxidation and require extra caution.

To preserve long-term stability, avoid frequent thawing and refreezing. A practical method is to divide the total peptide quantity into smaller aliquots for individual experimental use. This approach minimizes repeated exposure to air and temperature changes, thereby maintaining peptide integrity over time.

Storing Peptides In Solution

Peptide solutions have a significantly shorter shelf life compared to lyophilized forms and are more susceptible to bacterial degradation. Peptides containing cysteine (Cys), methionine (Met), tryptophan (Trp), aspartic acid (Asp), glutamine (Gln), or N-terminal glutamic acid (Glu) residues tend to degrade more rapidly when stored in solution.

If storage in solution is unavoidable, it is recommended to use sterile buffers with a pH between 5 and 6. Aliquoting the solution is essential to minimize freeze-thaw cycles. Under refrigerated conditions at 4°C (39°F), most peptide solutions remain stable for up to 30 days. However, peptides known to be less stable should be kept frozen when not in immediate use.

Peptide Storage Containers

Storage containers for peptides must be clean, clear, durable, and chemically resistant, and sized appropriately to minimize excess air space. Both glass and plastic vials are suitable:

• Polystyrene vials are clear but have limited chemical resistance.
• Polypropylene vials are more chemically resistant though usually translucent.
• High-quality glass vials offer the best combination of clarity, stability, and chemical inertness.

While peptides are often shipped in plastic vials to prevent breakage, they can be safely transferred between glass and plastic vials to suit specific storage or handling requirements.

Peptide Storage Guidelines: General Tips

When storing peptides, follow these best practices to maintain stability and prevent degradation:

• Store peptides in a cold, dry, and dark environment.
• Avoid repeated freeze-thaw cycles.
• Minimize exposure to air to reduce oxidation risk.
• Protect peptides from light.
• Do not store peptides in solution long term; keep them lyophilized whenever possible.
• Aliquot peptides based on experimental needs to prevent unnecessary handling.