Transmembrane AMPA receptor regulatory protein gamma-8 (TARP-γ8) (TARP-γ8)

Transmembrane AMPA receptor regulatory protein gamma-8 (TARP-γ8) is a specialized auxiliary subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, primarily encoded by the CACNG8 gene [1.5.2, 1.5.4]. It plays a critical role in the central nervous system by regulating the trafficking, surface expression, and gating properties of AMPA receptors, which mediate the majority of fast excitatory synaptic transmission [1.3.3, 1.5.1]. TARP-γ8 is uniquely enriched in the forebrain, particularly within the hippocampus and cortex, distinguishing it from other TARP isoforms like γ-2 (stargazin) found in the cerebellum [1.3.2, 1.4.3]. This regional specificity makes the TARP-γ8/AMPA receptor complex a high-priority therapeutic target for neurological conditions such as temporal lobe epilepsy and chronic pain [1.3.1, 1.3.2]. Selective negative allosteric modulators, including LY3130481 and JNJ-55511118, have been developed to inhibit these specific receptor complexes, offering the potential for potent anticonvulsant and analgesic activity without the debilitating motor side effects associated with non-selective AMPA receptor antagonists [1.4.1, 1.6.3]. However, because TARP-γ8 is essential for long-term potentiation and synaptic plasticity, therapeutic modulation carries potential risks for cognitive and memory impairment [1.5.1, 1.5.3].

Other names

CACNG8Calcium voltage-gated channel auxiliary subunit gamma 8Neuronal voltage-gated calcium channel gamma-8 subunitVoltage-dependent calcium channel gamma-8 subunitTARP gamma-8

Selective negative allosteric modulation of TARP-γ8-containing AMPA receptors