IDH1 and glioma: The mechanisms for this accumulation are as follows: (1) glioma cells overexpress the cystine-glutamate transporter, which increases extracellular glutamate concentrations [11, 12, 33], (2) decreased expression of EAAT1 and EAAT2 (two excitatory amino acid transporters) in tumor cell membranes and peritumoral activated microglia lead to reduced glutamate reuptake [12, 33], and (3) although IDH mutations do not directly produce glutamate, they can lead to the production of D-2-hydroxyglutarate, which stimulates glutamate receptors due to its structural similarity to glutamate [34, 35].