. 2024 Sep 9;13(17):1509. doi: 10.3390/cells13171509

Table 1.

In vitro supplementation of NAD⁺ precursors and small molecules.

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]
SOD1^G93A	VSC 4.1 cells	Resveratrol	10 µM	2 days	Improved survival; increased ATP, MFN2 and PGC-1α	[97]
SOD1^G93A	Cortical neurons	Resveratrol	250 nM	2 days	Reduced SOD1^G93A toxicity	[98]
Sporadic	hiPSC MN	NAM	0.5 mM	7 days	Improved survival; increased mitochondrial NAD⁺ and respiration; higher CHOP and sXBP1 expression	[99]
Sporadic	hiPSC MN	C12	5 µM	7 days		[99]
SOD1^G93A	SC-astrocytes	NR	5 mM	1 day	Increased NAD⁺; decreased astrocyte toxicity; reduced mitochondrial ROS production; higher HMOX1 and SRXN1 expression	[90,91]
SOD1^G93A	SC-astrocytes	NMN	5 mM	1 day		[90,91]
TDP-43^A315T	CS-MN	NMN	1 µM	3 days	Increased axon length and neurite intersections and improved mitochondrial ultrastructure	[93]
SOD1^G93A	SC-MN	NMN	2 mM	2 days	Elevated GSH and NAD⁺, increased neurite length/complexity; improved survival;higher nuclear/cytoplasmic TDP-43 ratio	[94]
SOD1^D90A	hiPSC MN
wtTDP-43 OE	SC-MN

Small molecules: resveratrol, SIRT1 activator; C12, SIRT3 activator. Precursors: NAD⁺, nicotinamide adenine dinucleotide; NAM, nicotinamide; NR, nicotinamide riboside; NMN, nicotinamide mononucleotide. MFN2, mitofusion 2; PGC-1α, peroxisome proliferator-activated receptor gamma coactivator 1-alpha; CHOP, C/EBP homologous protein; sXBP1, spliced X-box binding protein 1; HMOX1, heme oxygenase 1; SRXN1, sulfiredoxin 1.