Glutamate receptor 1 (GluA1) (GluA1)

Glutamate receptor 1 (GluA1), encoded by the GRIA1 gene, is a primary subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, which is a ligand-gated ionotropic glutamate receptor [1, 6]. It plays a fundamental role in the central nervous system by mediating fast excitatory synaptic transmission through the influx of sodium and potassium ions upon glutamate binding [5, 11]. GluA1 is particularly critical for synaptic plasticity, including long-term potentiation (LTP), which is the cellular basis for learning and memory [1, 11]. Dysregulation or mutations in the GRIA1 gene are associated with various neurological and psychiatric disorders, such as epilepsy, Alzheimer's disease, schizophrenia, and intellectual developmental disorders [9, 11, 15]. Pharmacologically, GluA1-containing receptors are targeted by drugs like perampanel, a non-competitive antagonist used to treat seizures by dampening excessive excitatory signaling [15, 16]. However, therapeutic modulation of this target is associated with significant safety concerns, including severe neuropsychiatric side effects like aggression and irritability, as well as sedation and dizziness [16].

Other names

GRIA1GLUR1GLURAGluR-1AMPA-selective glutamate receptor 1GluR-AGluR-K1Glutamate ionotropic receptor AMPA type subunit 1

Non-competitive antagonism of the AMPA receptor, which reduces the frequency of channel opening and inhibits excitatory neurotransmission [15, 16]. Some research compounds act as competitive antagonists or positive allosteric modulators [3, 10].