Gamma-aminobutyric acid type A receptor subunit alpha-5 and subunit pi (GABRA5/GABRP)

Gamma-aminobutyric acid type A receptor subunit alpha-5 (GABRA5) and subunit pi (GABRP) are integral components of the GABA-A receptor complex, a pentameric ligand-gated ion channel that mediates inhibitory neurotransmission [4, 12]. GABRA5 is primarily localized in the hippocampus, where it mediates tonic inhibition and plays a pivotal role in regulating cognitive processes such as learning and memory [1, 2]. Consequently, GABRA5 is a major therapeutic target for cognitive enhancement in conditions like Alzheimer's disease and schizophrenia, with selective inverse agonists like basmisanstat being developed to reduce inhibitory tone [2, 18]. GABRP is expressed in both the central nervous system and peripheral tissues and is significantly upregulated in several cancers, including triple-negative breast cancer and glioma [7, 11]. In these oncological contexts, GABRP promotes tumor cell migration and immune evasion by modulating signaling pathways like PI3K/AKT and ERK1/2 [7, 11]. Recent research also identifies both GABRA5 and GABRP as core targets for treating cognitive dysfunction in type 2 diabetes, highlighting their diverse roles in both neurological and systemic diseases [8, 13].

Other names

GABRA5GABRPGABA(A) receptor subunit alpha-5GABA(A) receptor subunit piGABA receptor alpha-5GABA receptor pi

Negative allosteric modulation (inverse agonism) of GABRA5-containing receptors to enhance cognition; inhibition of GABRP-mediated signaling to suppress tumor progression and immune evasion.