Glutamate receptor ionotropic, AMPA 2 (GluA2)

Glutamate receptor ionotropic, AMPA 2 (GluA2) is a critical subunit of the AMPA-type ionotropic glutamate receptors, which mediate the majority of fast excitatory neurotransmission in the mammalian central nervous system [1, 13]. A defining feature of GluA2 is that its pre-mRNA undergoes nearly 100% efficient adenosine-to-inosine (A-to-I) RNA editing at the Q/R site, which converts a glutamine codon to an arginine codon; this modification renders GluA2-containing receptors impermeable to calcium, thereby protecting neurons from calcium-mediated excitotoxicity [3, 12, 15]. In several neurological conditions, such as amyotrophic lateral sclerosis (ALS) and ischemia, defective RNA editing or reduced GluA2 expression leads to the formation of calcium-permeable AMPA receptors, which contribute to motor neuron death and neurodegeneration [3, 19, 21]. Conversely, gain-of-function mutations or overactivity of these receptors are linked to epilepsy and neurodevelopmental disorders [9, 16]. Clinically, GluA2 is a key therapeutic target for antiepileptic drugs, most notably perampanel, a selective non-competitive antagonist that binds to an allosteric site to reduce excitatory signaling [5, 6, 7]. Research also explores positive allosteric modulators, known as ampakines, for potential use in cognitive enhancement and respiratory depression [13, 20].

Other names

GRIA2GluR2GluRBGLUR2GluR-K2HBGR2AMPA-selective glutamate receptor 2Glutamate receptor 2

Non-competitive allosteric antagonism, competitive antagonism, positive allosteric modulation