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Multi-targeted Effect of Nicotinamide Mononucleotide on Brain Bioenergetic Metabolism

  • Nina Klimova
  • Tibor KristianEmail author
Original Paper

Abstract

Dysfunctions in NAD+ metabolism are associated with neurodegenerative diseases, acute brain injury, diabetes, and aging. Loss of NAD+ levels results in impairment of mitochondria function, which leads to failure of essential metabolic processes. Strategies to replenish depleted NAD+ pools can offer significant improvements of pathologic states. NAD+ levels are maintained by two opposing enzymatic reactions, one is the consumption of NAD+ while the other is the re-synthesis of NAD+. Inhibition of NAD+ degrading enzymes, poly-ADP-ribose polymerase 1 (PARP1) and ectoenzyme CD38, following brain ischemic insult can provide neuroprotection. Preservation of NAD+ pools by administration of NAD+ precursors, such as nicotinamide (Nam) or nicotinamide mononucleotide (NMN), also offers neuroprotection. However, NMN treatment demonstrates to be a promising candidate as a therapeutic approach due to its multi-targeted effect acting as PARP1 and CD38 inhibitor, sirtuins activator, mitochondrial fission inhibitor, and NAD+ supplement. Many neurodegenerative diseases or acute brain injury activate several cellular death pathways requiring a treatment strategy that will target these mechanisms. Since NMN demonstrated the ability to exert its effect on several cellular metabolic pathways involved in brain pathophysiology it seems to be one of the most promising candidates to be used for successful neuroprotection.

Keywords

Nicotinamide adenine dinucleotide Nicotinamide mononucleotide Mitochondria Acetylation Brain 

Notes

Acknowledgements

The project described was supported by Award Number I01BX000917 from the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development to TK.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. 1.Veterans Affairs Maryland Health Care SystemBaltimoreUSA
  2. 2.Department of Anesthesiology, Center for Shock, Trauma and Anesthesiology Research, School of MedicineUniversity of MarylandBaltimoreUSA

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