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Excitatory amino acid transporter 1 (EAAT1) (EAAT1 (also known as GLAST))

Target
EAAT1 (also known as GLAST)
Molecular classification
Transporter
01

Overview

The glial glutamate aspartate transporter, commonly known as excitatory amino acid transporter 1 (EAAT1) or GLAST (SLC1A3), is a sodium-dependent transporter predominantly expressed in glial cells, including astrocytes and Bergmann glia in the cerebellum. It plays a critical role in clearing glutamate from the synaptic cleft and extrasynaptic spaces by facilitating reuptake into glia, thereby maintaining low extracellular glutamate levels to prevent excitotoxicity and regulate glutamatergic signaling. EAAT1 co-transports glutamate with 2-3 Na+ ions and 1 H+, counter-transports 1 K+, and functions as a trimer where each monomer can independently transport substrate. Once internalized, glutamate is converted to glutamine via glutamine synthetase in astrocytes, supporting the glutamate-glutamine cycle that recycles the neurotransmitter back to neurons. Dysregulation of EAAT1 contributes to glutamatergic dysfunction implicated in neurodegenerative diseases and psychiatric disorders, with altered expression, trafficking, and glycosylation affecting its activity. While no approved drugs directly target EAAT1, inhibitors like TBOA are used in research to study transport mechanisms.

Other names
GLASTSLC1A3glutamate aspartate transporterL-glutamate/L-aspartate transporter
02

Mechanism of action

Competitive inhibition of glutamate uptake, Na+-dependent transport blockade

03

Biological functions

Regulates extracellular glutamate concentrationsglutamate reuptake into glial cellsglutamate-glutamine cycleprevents excitotoxicity
04

Disease associations

Neurodegenerative diseasepsychiatric disordersexcitotoxicity-related conditions
05

Safety considerations

Potential disruption of glutamate homeostasis leading to excitotoxicity or impaired neurotransmissionaltered expression in disease states
06

Interacting drugs

TBOA (dl-threo-β-benzyloxyaspartate)

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