Excitatory amino acid transporter (EAAT)

Glutamate transporters are a broad class of membrane proteins, primarily categorized into plasma membrane excitatory amino acid transporters (EAATs) and vesicular glutamate transporters (VGLUTs) (Danbolt, 2001). EAATs (EAAT1-5) are responsible for removing glutamate from the synaptic cleft to terminate signal transmission and prevent excitotoxicity (Rose et al., 2018). EAAT2 (GLT-1) is the most abundant subtype in the brain and is a major focus for therapeutic intervention in neurodegenerative diseases like Amyotrophic Lateral Sclerosis (ALS) (Jensen et al., 2015). VGLUTs (VGLUT1-3) package glutamate into synaptic vesicles for release, playing a distinct but complementary role in excitatory signaling (Liguz-Lecznar & Skangiel-Kramska, 2007). Dysregulation of these transport systems leads to excessive extracellular glutamate, contributing to neuronal death in conditions such as stroke, epilepsy, and Alzheimer's disease (Bak et al., 2006). Current pharmacological strategies include the use of Riluzole to enhance EAAT2 activity and experimental small molecules to modulate transporter expression (Soni et al., 2014). Safety concerns involve maintaining the delicate balance of excitatory neurotransmission to avoid psychiatric side effects or seizures (Kim et al., 2011). Monitoring EAAT function in vivo remains a challenge, though novel PET imaging ligands like [11C]MAP432 are currently under development to serve as biomarkers for target engagement (Himi et al., 2020).

Other names

Glutamate transporterExcitatory amino acid transporterEAATSolute carrier family 1SLC1AGLT-1GLASTEAAC1Vesicular glutamate transporterVGLUT

Upregulation of transporter expression, enhancement of glutamate uptake activity, and competitive inhibition of glutamate binding.