Table 2.
In vivo administration of interventions targeting NAD+ metabolism.
| Model | Route | Treatment | Dose | Duration | Benefits | Ref. |
|---|---|---|---|---|---|---|
| SOD1G93A | Sub-cutaneouspump | NAM | 7.4 mg/kg BW/day | 12 weeks | Longer rotarod retention; lower neurological score; increased NAM in CSF | [82] |
| SOD1G93A | i.p | P7C3 | 20 mg/kg BW/day | 7 weeks | Improved rotarod retention and stride length and reduced MN loss | [92] |
| SOD1G93A | Diet | Resveratrol | 160 mg/kg BW/day | 8 weeks | Faster treadmill walking speed; increased lifespan and MN survival; higher CMAP and MEP amplitude; decreased p53 acetylation | [103] |
| SOD1G93A | Diet | NR | 400 mg/kg BW/day | 9 weeks | Improved body weight and grip strength; decreased Cxcl10/Ccl5/Ptgs2/Tnf; reduced Chrna1 and Uchl1 | [85] |
| SOD1G93A | Drinking water | NR | 400 mg/kg BW/day | 10 weeks | Increased Vimentin+ and DCX+ neurons | [104] |
| SOD1G93A | Oral gavage and diet | NR (w/ and w/o PT/NAC) | 185 mg/kg BW/day | 14 weeks | Prolonged survival; higher nerve conduction amplitude and velocity; increased NAD+; decreased TNF-α/IL2/IL6 and mitochondrial Ca2+ | [77] |
| FUSS57Δ | Growth media | 3-AB | 20 µM | 9 days | Decreased axonal breaks, slower paralysis onset | [105] |
| SOD1G93A | Olaparib | 500 nM | ||||
| TDP-43A315T | Veliparib | 1 µM | ||||
| SOD1G93A | Oral gavage and diet | NR (w/ PT+Ibu) | 185 mg/kg BW/day | 14 weeks | Longer rotarod retention and lifespan; improved MN survival; reduced TNF-α/IFNγ/IL1-β in CSF | [89] |
| FUSR521C | ||||||
| SOD1G93A | Diet | NMN | 400 mg/kg BW/day | 10 weeks | Improved evoked and spontaneous EPP amplitude and increased NMJ plasticity and morphology | [76] |
Small molecules: P7C3, NAMPT activator; resveratrol, SIRT1 activator; C12, SIRT3 activator; PT/ pterostilbene, SIRT1 activator; NAC/N-acetyl-cysteine, thiol donor; 3-AB/Olaparib/Veriparib, PARP inhibitors; Ibu/ibudilast, phosphodiesterase inhibitor. Precursors: NAM, nicotinamide; NR, nicotinamide riboside; NMN, nicotinamide mononucleotide; i.p., intraperitoneal injection; MN, motor neuron; Cxcl10, C-X-C motif chemokine ligand 10; Ccl5, C-C motif chemokine ligand 5; Ptgs2, prostaglandin-endoperoxide synthase 2; TNF-α, tumor necrosis factor alpha; IL2, interleukin 2; IL6, interleukin 6; IFNγ, interferon gamma; IL1-β, interleukin 1 beta.