CN-mediated impairment of glutamate uptake in astrocytes. (A) In healthy nervous tissue, astrocytes remove excess glutamate from the extracellular milieu using EAATs. (B) Pro-inflammatory cytokines and Aβ cause hyperactivation of CN in astrocytes leading to the activation of NFAT and NFΚB transcription factors. Together, and possibly individually, NFATs and NFΚB suppress the transcription of EAATs. Loss of EAAT protein is associated with reduced glutamate uptake, higher extracellular glutamate levels, and increased excitotoxicity.