NMN: the Dawn for Patients with Amyotrophic Lateral Sclerosis

NMN: the Dawn for Patients with Amyotrophic Lateral Sclerosis



1. Introduction

Amyotrophic lateral sclerosis (ALS) is a progressive fatal neurodegenerative disease that affects the motion-related nerve cells in the brain and spinal cord. The disease is featured by the death of upper and lower motor neurons (MNs) and manifested by progressive muscle atrophy and weakness, culminating in immobility to paralysis, with the body gradually frozen as if by ice. Patients with this disorder generally have a low survival rate and life quality.

At present, there is no effective way to cure this disease, but early invention has a positive significance in improving the symptoms of patients and delaying the progression of disease. Remarkably, dietary NMN supplementation has been uncovered to be beneficial against ALS, which can enhance the motor and function of neuromuscular junctions (NMJs) in ALS, bringing a glimpse of hope for ALS patients.

2. The improved healthspan and reduced motor dysfunction in ALS mice post dietary NMN supplementation

The median lifespan of ALS mice administrated with or without NMN is 143 days and 138 days, respectively, hinting that NMN supplementation in diet has a modest effect on lifespan extension. Relative to those without dietary NMN supplementation, NMN-treated ALS mice shows a slower motor impairment in both rotarod and hanging wire tests, with a two-week delay in dysfunction, despite no difference in body weight loss during testing period.



When compared with those in the absence of dietary NMN supplementation, ALS mice administrated with NMN are more active, with increased travel distance, elevated mean speed and reduced immobile time. In addition, NMN diet prevents ALS-induced gait impairments, as manifested by the improved forelimb and hindlimb stride length in NMN-treated ALS mice.

3. The alleviating effect of NMN on the function of NMJs in ALS

NMJs are one of the earliest affected site in ALS, which are benefited greatly from NMN diet. In addition to improving the length and breadth of the motor endplate, dietary NMN supplementation also ameliorates the impairment of NMJ function and reduce the semitendinosus muscle mass in ALS mice. Furthermore, NMN conspicuously elevates the innervation ratio of NMJs in ALS mice.


Dietary NMN supplementation strengthens synaptic function at NMJ in ALS, while diminishing NMJ and intermyofibrillar (IMF) mitochondrial abnormalities. With a great detail, NMN prominently increases Feret's diameter of mitochondria and restores mitochondria circularity in ALS mice.

4. Conclusion

Dietary NMN supplementation can modestly extend lifespan and significantly enhance healthspan by improving motor performance and NMJ function in ALS mice, opening up new opportunities for the future treatment of ALS.

Reference

Lundt S, Zhang N, Polo-Parada L, et al. Dietary NMN supplementation enhances motor and NMJ function in ALS. Exp Neurol. Published online January 22, 2024. doi:10.1016/j.expneurol.2024.114698

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