Gamma-aminobutyric acid type A receptor alpha-5 beta-2 gamma-2 (GABA_A receptor α5β2γ2) (GABA_A receptor α5β2γ2)

The Gamma-aminobutyric acid type A receptor alpha-5 beta-2 gamma-2 (GABA_A receptor α5β2γ2) is a specific subtype of the heteropentameric ligand-gated chloride channel that mediates fast inhibitory neurotransmission in the central nervous system. Unlike many other GABA-A subtypes that are primarily synaptic, alpha-5 containing receptors are predominantly located extra-synaptically in the hippocampus, where they mediate tonic inhibition and play a critical role in regulating synaptic plasticity and memory formation (PMID: 21610137). Because of its localized expression in brain regions associated with cognition, this receptor is a high-priority target for the treatment of cognitive deficits associated with Alzheimer's disease, Down syndrome, and schizophrenia (PMID: 24761741). Therapeutic strategies often involve negative allosteric modulators (NAMs) to enhance cognition by reducing tonic inhibition, or positive allosteric modulators (PAMs) for potential antidepressant or anxiolytic effects without the sedative side effects typically associated with alpha-1 containing receptors (PMID: 30115630, PMID: 28439118).

Other names

α5β2γ2 GABA-A receptorGABRA5-GABRB2-GABRG2 complexAlpha-5 beta-2 gamma-2 GABA-A receptorGABA(A) receptor subunit alpha-5/beta-2/gamma-2

Positive or negative allosteric modulation of the GABA-A receptor complex, which alters the frequency or duration of chloride channel opening in response to GABA binding, thereby modulating neuronal hyperpolarization and excitability (PMID: 24761741, PMID: 30115630).