Potential Therapeutic Interventions Targeting NAD+ Metabolism for ALS
Abstract
:1. Introduction
2. NADase Activity and Cellular Function
3. ALS and NAD+ Metabolism
4. Therapeutic Interventions of ALS by NAD+ Precursors
Model | Cell Type | Treatment | Dose | Duration | Benefits | Ref. |
---|---|---|---|---|---|---|
Sporadic | SC-MN | NAD+ | 10 mM | 14 days | Increased neurite length | [95] |
TDP-43 KD | SC-MN | NAM | 0.1 mM | 6 days | Axon outgrowth and increased protein synthesis | [96] |
SOD1G93A | VSC 4.1 cells | Resveratrol | 10 µM | 2 days | Improved survival; increased ATP, MFN2 and PGC-1α | [97] |
SOD1G93A | Cortical neurons | Resveratrol | 250 nM | 2 days | Reduced SOD1G93A toxicity | [98] |
Sporadic | hiPSC MN | NAM | 0.5 mM | 7 days | Improved survival; increased mitochondrial NAD+ and respiration; higher CHOP and sXBP1 expression | [99] |
C12 | 5 µM | |||||
SOD1G93A | SC-astrocytes | NR | 5 mM | 1 day | Increased NAD+; decreased astrocyte toxicity; reduced mitochondrial ROS production; higher HMOX1 and SRXN1 expression | [90,91] |
NMN | 5 mM | |||||
TDP-43A315T | CS-MN | NMN | 1 µM | 3 days | Increased axon length and neurite intersections and improved mitochondrial ultrastructure | [93] |
SOD1G93A | SC-MN | NMN | 2 mM | 2 days | Elevated GSH and NAD+, increased neurite length/complexity; improved survival;higher nuclear/cytoplasmic TDP-43 ratio | [94] |
SOD1D90A | hiPSC MN | |||||
wtTDP-43 OE | SC-MN |
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] |
5. Future Perspectives
Author Contributions
Funding
Conflicts of Interest
References
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Lundt, S.; Ding, S. Potential Therapeutic Interventions Targeting NAD+ Metabolism for ALS. Cells 2024, 13, 1509. https://doi.org/10.3390/cells13171509
Lundt S, Ding S. Potential Therapeutic Interventions Targeting NAD+ Metabolism for ALS. Cells. 2024; 13(17):1509. https://doi.org/10.3390/cells13171509
Chicago/Turabian StyleLundt, Samuel, and Shinghua Ding. 2024. "Potential Therapeutic Interventions Targeting NAD+ Metabolism for ALS" Cells 13, no. 17: 1509. https://doi.org/10.3390/cells13171509