CHRNB2

The CHRNB2 gene encodes the neuronal acetylcholine receptor subunit beta-2 (β2-nAChR), a critical component of nicotinic acetylcholine receptors in the central and peripheral nervous systems. These receptors function as ligand-gated ion channels, mediating synaptic transmission by binding acetylcholine or nicotine, triggering conformational changes that permit cation influx (Na⁺, K⁺, Ca²⁺). β2-containing nAChRs predominantly localize to presynaptic and postsynaptic membranes, modulating neurotransmitter release and synaptic plasticity. Key pathways include cholinergic signaling, neuroinflammation regulation, and nicotine addiction circuits. The β2 subunit often partners with α4 (forming α4β2 receptors), the most abundant high-affinity nicotine-binding subtype in the brain, implicated in cognitive functions and reward mechanisms.
Mutations in CHRNB2 are linked to autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) and suspected in schizophrenia susceptibility due to disrupted cortical inhibition. Altered β2-nAChR expression correlates with Parkinson’s disease progression and nicotine dependence. Pharmacologically, α4β2 agonists like varenicline (Champix®) are approved for smoking cessation, while allosteric modulators and subtype-selective antagonists are under investigation for epilepsy and cognitive disorders. Recent trials explore β2-targeted therapies for neuropsychiatric conditions, leveraging its role in dopaminergic and glutamatergic pathway cross-talk.