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Neurodegenerative diseases (NDDs) are a global health challenge that currently affects more than 80 million people, and the number of patients is expected to double in the next 20-30 years. These diseases include Parkinson's disease (PD) and Alzheimer's disease (AD), and there is currently no effective treatment to delay or prevent disease progression. The pathological characteristics of NDDs include protein misfolding and aggregation, mitochondrial dysfunction, energy metabolism defects, protein homeostasis imbalance, and neuroinflammation.
NAD is a molecule essential to life. As a key redox coenzyme in nutrient and energy metabolism pathways, NAD is constantly converted between oxidized (NAD+) and reduced (NADH) forms. NAD+ is also a substrate for multiple signaling reactions, participating in DNA repair, epigenetic regulation of gene expression, and calcium signaling. With age, NAD levels decline, and this decline is believed to be associated with the occurrence and development of age-related diseases. Therefore, enhancing NAD metabolism by supplementing precursors shows potential for anti-aging and neuroprotection.
NAD biosynthesis can be initiated by a variety of precursors or biosynthetic intermediates. Currently, enhancing NAD biosynthesis by supplementing precursors is the most commonly used method in clinical applications. Commonly used precursors include nicotinamide riboside (NR) and Nicotinamide Mononucleotide (NMN).
1. In induced pluripotent stem cell (iPSC)-derived neurons and Drosophila models, NR has been shown to improve mitochondrial function in PD associated with glucocerebrosidase (GBA) and rescue the phenotype of the disease.
2. In the AD model of Caenorhabditis elegans, NMN supplementation restored defective mitochondrial autophagy, a phenotype also observed in human AD brains, and alleviated cognitive decline.
NAD enhancement therapy has shown great potential in the treatment of neurodegenerative diseases, and preclinical studies have achieved positive results. With the continuous advancement of related research, NAD enhancement therapy is expected to bring breakthroughs in the treatment of neurodegenerative diseases
Dölle C, Tzoulis C. NAD augmentation as a disease-modifying strategy for neurodegeneration[J]. Trends in Endocrinology & Metabolism, 2025.
*Special note - This article is for informational purposes only and cannot replace a doctor's treatment diagnosis and advice. It should not be regarded as a recommendation or proof of efficacy of the medical products involved. If it involves disease diagnosis, treatment, and rehabilitation, please be sure to go to a professional medical institution to seek professional advice.
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