HOW DOES NAD+ AFFECT OUR BRAIN?

Key Pointers

NAD+ affects the brain by:

  • Neuronal development and neuro-protective.
  • Role in senile changes in the brain.
  • Acting as a transmitter.
  • Having a role in neurodegenerative disorders.

NAD+ is an abundant molecule in organisms and plays an important function in the cell. The new research show that dysfunctions in NAD+ metabolism lead to many ailments, such as neurodegenerative disorders, senile changes, diabetes, and brain injury. The decline in the NAD+ levels causes failure of metabolic processes due to impairment of mitochondrial functions. The brain requires a sufficient amount of energy to perform its functions. The energy level goes up during intensive brain activity. The NAD+ in the mitochondria helps in energy production for the brain cells. The deficiency of NAD in brain cells leads to a decrease in energy generation, ultimately resulting in brain injury.


Increasing the level of NAD+ to the body is very useful in improving brain function and reducing stress. An increase in NAD+ levels boosts the metabolic energy in the brain cells to perform its functions smoothly.


Increasing the level of NAD+ to the body is useful in improving memory, treating addictions effectively, whipping fatigue, and maintaining a sharp mind.


The current evidence shows that NAD+ plays a significant role in learning, memory, and neurotransmission in the brain. It is also vital in brain aging and cell damage. NAD+ can cross the blood, brain barrier, and increased NAD+ can decrease tissue damage. The emerging role of nicotinamide adenine dinucleotide in the protection of axonal degeneration is crucial for many neurodegenerative disorders, like Alzheimer's disease. Other neurodegenerative diseases such as Parkinson's disease and multiple sclerosis are linked with the dysfunction of mitochondria due to oxidative stress. PARP1 (poly-ADP-ribose polymerases) can mediate cell death in the brain in patients with Alzheimer's disease, multiple sclerosis, and Parkinson's disease.


The NMN adenylyltransferase (NMNAT) is an enzyme that converts nicotinamide mononucleotide into NAD+. The augmented activity of NMNAT leads to the protection of neurons that undergo Wallerian degeneration. The NMNAT increases the NAD+ level in the brain that activates the NAD-dependent protein deacetylase sirtuin 1 (SIRT1) making it a neuroprotective mediator. Nicotinamide also plays a role in the peripheral nervous system in which NMNAT acts as a molecular overseer to inhibit protein misfolding in peripheral neurons, due to multiple reasons. Beta-NAD is known to be an inhibitory neurotransmitter in the gastrointestinal smooth muscles, released by the activation of enteric nerves.


The metabolism of NAD+ has a direct role in the development, growth, and survival of neurons in the CNS. Nicotinamide speeds up the transformation of embryonic stem cells to neural progenitors thus having a central role in neuronal development. NAD+ acts as a hallmark of brain aging that occurs by the depletion of NAD+ and amassing of damaged products as the result of oxidative stress and reactive oxygenous species in the aging brain. Thus the level of NAD+ is related to the brain aging process.


NAD+ is not only a coenzyme but also an important cosubstrate that participates in different chemical reactions of the body.


Conclusion

NAD+ is liable to provide energy to every cell of the body including the brain through its role in the mitochondrial energy production pathway. It also acts as a neurotransmitter in smooth muscle. NAD+ is a neuroprotective substance and an imbalance in its level causes many neuronal diseases, like Alzheimer's disease.


References

  1. Bezprozvanny I, and Mattson MP (2008). Neuronal calcium mishandling and the pathogenesis of Alzheimer’s disease. Trends Neurosci. 31, 454–463.
  2. Birkmayer JG, Vrecko C, Volc D, and Birkmayer W (1993). Nicotinamide adenine dinucleotide (NADH)–a new therapeutic approach to Parkinson’s disease. Comparison of oral and parenteral application. Acta Neurol. Scand. Suppl 146, 32–35
  3. Braidy N, Guillemin GJ, Mansour H, Chan-Ling T, Poljak A, and Grant R (2011). Age-related changes in NAD+ metabolism oxidative stress and Sirt1 activity in Wistar rats. PLoS One 6, e19194.