Table 1.

Summary of model specific changes in metabolism found in NMDs.

Disease	Model	Findings
ALS	Neuronal—Patients	Decreased glucose uptake in motor cortex [76,77] Disrupted mitochondria in spinal cord samples [53,78,79,80,81] Increased mutated mtDNA and decreased mtDNA in cortex [82]
	Neuronal—in vivo	Defects in glucose uptake and ATP production from defective mitochondria in SOD1 models [86,87] Increased mitochondrial malfunction and altered morphology [90] Defects in mitochondrial respiration and increased oxidative stress in TDP43 mouse model [91] TDP43 Drosophila model increased PFK as compensatory [92]
	Neuronal—in vitro	iPSCs show increased glycolysis and decreased mitochondrial respiration [94,95] Decreased PPP intermediates resulting in oxidative stress [98]
	Skeletal—Patients	Mitochondrial dysfunction via COX-negative fibers in ALS patient muscle biopsies [99]
	Skeletal—in vivo	Reduction of mitochondrial proteins [100] Defects in mitochondrial dynamics before disease onset [101,102] Decreased glycolytic pathway activation [2]
PLS	Neuronal—Patients	Hypometabolism in the precentral gyrus [8,103]
SMA	Neuronal—in vivo	SMA mouse model shows decreased mitochondrial respiration [104]
Kennedy’s Disease	Neuronal—in vitro	Decreased mitochondrial genes and increased ROS [105]
HSP	Skeletal—Patients	SPG28 subtype decreased mitochondrial DNA and altered mitochondrial morphology [106]
	Neuronal—in vitro	SPG7 subtype olfactory neurosphere-derived cells demonstrated fragmented mitochondria, decreased mitochondrial membrane potential, reduced oxidative phosphorylation, reduced ATP concentration and increased oxidative stress [107] IPSCs derived from SPG11 and SPG48 subtypes show decreased mitochondrial length, density and ATP levels [108]