Excitatory amino acid transporter (EAAT) (EAAT)

The glutamate uptake system, primarily mediated by the excitatory amino acid transporter (EAAT) family, is the principal mechanism for removing the excitatory neurotransmitter glutamate from the extracellular space in the central nervous system (Danbolt, 2001, Progress in Neurobiology). This system is crucial for terminating synaptic transmission and maintaining extracellular glutamate at sub-micromolar levels to prevent excitotoxicity, a process where excessive glutamate leads to neuronal overstimulation and death (Jensen et al., 2015, Neurochemistry International). There are five human EAAT subtypes (EAAT1-5), with EAAT2 (GLT-1) being responsible for the majority of glutamate clearance in the forebrain (UniProt P43004). Dysfunction or downregulation of these transporters is a hallmark of several neurodegenerative and psychiatric conditions, including amyotrophic lateral sclerosis (ALS), Alzheimer's disease, and epilepsy (Kong et al., 2014, Journal of Biological Chemistry). Pharmacological modulation of the glutamate uptake system, particularly through the upregulation of EAAT2 expression by drugs like riluzole or experimental compounds like LDN-212320, represents a significant therapeutic strategy for neuroprotection (NIH/NCBI Gene ID 6506). However, achieving subtype specificity and effective blood-brain barrier penetration remains a challenge for drug development in this area.

Other names

Glutamate uptake systemGlutamate transporterSolute carrier family 1SLC1Sodium-dependent glutamate transporterGLT-1GLASTEAAC1

Modulation of glutamate uptake through transcriptional upregulation of transporter proteins (e.g., EAAT2) or direct allosteric activation of transport kinetics (Danbolt, 2001; Kong et al., 2014).