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One unresolved question in ALS is why the neurons most susceptible to the altered/deficient EAAT2 (and neurodegeneration) come from two different populations which do not have much in common: The lower motor neurons in the spinal cord are cholinergic and project peripherally while the upper motor neurons are glutamatergic, excitatory, reside in the cerebral neocortex and target the brain stem and spinal cord (corticobulbar and corticospinal tracts)

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Due to cardiomyocytes requiring massive energy demands, they are rich in mitochondria standing out from the rest of the cell type [15, 16], which makes them very sensitive to oxidative stress damage