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LDN-0212320 is an activator of excitatory amino acid transporter 2 (EAAT2) that increases expression of EAAT2 in PA-EAAT2 cells in a concentration- and time-dependent manner (EC50 = 1.83 μM).1 It selectively increases EAAT2 protein levels over EAAT1 and EAAT3 protein levels and increases glutamate uptake in primary dissociated neuron and astrocyte mixed cultures when used at concentrations ranging from 1 to 3 μM. LDN-0212320 (3 μM) decreases neuronal loss and degeneration in primary dissociated neuron and astrocyte mixed cultures. In vivo, LDN-0212320 (40 mg/kg, i.p.) increases EAAT2 protein levels and glutamate uptake in mouse forebrain. It also delays motor function decline and increases lifespan in the SOD1G93A transgenic mouse model of amyotrophic lateral sclerosis (ALS).
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