Excitatory amino acid transporter 2 (EAAT2) (EAAT2)

Excitatory amino acid transporter 2 (EAAT2), also known as GLT-1 in rodents, is the primary glutamate transporter in the mammalian central nervous system, responsible for clearing over 90% of extracellular glutamate from the synaptic cleft (NIH, Wikipedia). By maintaining low extracellular glutamate concentrations, EAAT2 prevents overstimulation of glutamate receptors, which would otherwise lead to excitotoxic neuronal death (PubMed, ASM). Dysfunction or downregulation of EAAT2 is a hallmark of several neurodegenerative and neurological conditions, including amyotrophic lateral sclerosis (ALS), Alzheimer's disease, and epilepsy (NIH, ACS). Consequently, EAAT2 is a major therapeutic target for neuroprotection, with research focusing on small molecules that can induce its expression or enhance its activity (NIH, Future Med Chem). Drugs like ceftriaxone and riluzole have been shown to upregulate EAAT2, although clinical success in some indications like ALS has been limited (NIH, PubMed). Emerging strategies include the development of translational activators like LDN-212320 and positive allosteric modulators to restore glutamate homeostasis without the off-target effects of broad-spectrum antibiotics (Cayman Chem, R&D Systems).

Other names

SLC1A2GLT-1Glutamate transporter 1Solute carrier family 1 member 2HBGTExcitotoxic amino acid transporter 2

Upregulation of gene expression through transcriptional induction (e.g., via NF-kB or HSF1 pathways), translational activation, and competitive inhibition of glutamate reuptake.