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Buildup of excess intracellular Ca 2+ causes the dendrites to retract and leads to activation of hydrolytic enzymes, initiation of cytoskeletal degradation, and eventual apoptosis ( 2+ can also enter the mitochondria and lead to increased mitochondrial dysfunction, a vicious cycle of mitochondrial damage, oxidative stress, and glutamate-mediated excitotoxicity, and apoptosis of motor neurons (Figure 2B), a hallmark of ALS ( The reduction in astrocytic glutamate uptake in combination with reduced mitochondrial energy production is anticipated to result in a decrease in the rate of the glutamate glutamine neurotransmitter cycle and potentially neuronal glutamate concentration

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