NMN / NAD+ Precursors for ALS
Also known as: Nicotinamide mononucleotide, NR (Nicotinamide Riboside), NAD+ boosters
NAD+ depletion in ALS motor neurons contributes to mitochondrial failure and impaired DNA repair. NAD+ restoration may support neuronal survival.
Mechanism of Action
NMN is converted to NAD+ via NMNAT enzymes. NAD+ is essential for mitochondrial Complex I function, sirtuin-mediated gene regulation (SIRT1, SIRT3), and PARP-mediated DNA repair — all compromised in ALS. NAD+ depletion accelerates motor neuron death by impairing energy metabolism and stress response.
General mechanism: NAD+ precursor. Supports mitochondrial function (Complex I), sirtuin activity (SIRT1/3), DNA repair (PARP), and cellular energy metabolism.
Current Evidence
Preclinical studies show NAD+ boosting delays neurodegeneration in ALS models. Human trials are limited to safety and NAD+ level confirmation. The rationale is strong given the central role of NAD+ in neuronal energy metabolism.
Clinical Status: Preclinical for ALS. Multiple human safety trials for NAD+ precursors. Available as supplements.
Safety Profile
Well-tolerated at studied doses (1-2g/day NMN, 500-2000mg/day NR). No significant adverse effects in human trials. Not regulated as pharmaceuticals.
Key Research Questions
- What NAD+ precursor (NMN vs. NR) most effectively raises CNS NAD+ levels?
- Can NAD+ restoration synergize with riluzole's anti-excitotoxic mechanism?