Glutamate is an essential excitatory neurotransmitter regulating brain functions. Excitatory amino acid transporter (EAAT)-2 is one of the major glutamate transporters expressed predominantly in astroglial cells and is responsible for 90% of total glutamate uptake. Glutamate transporters tightly regulate glutamate concentration in the synaptic cleft. Dysfunction of EAAT2 and accumulation of excessive extracellular glutamate has been implicated in the development of several neurodegenerative diseases including Alzheimer’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. Analysis of the human EAAT2 promoter showed that NF-kB is an important regulator of EAAT2 expression in astrocytes. Screening of approximately 1,0 FDA-approved compounds led to the discovery that many b-lactam antibiotics such as ceftriaxone etc. are transcriptional activators of EAAT2 resulting in increased EAAT2 protein levels and produce neuroprotective effects.