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Target intelligence / Profile preview
Cholinergic receptor nicotinic alpha 4 subunit (CHRNA4)
- Target
- CHRNA4
- Molecular classification
- Receptor, Ion channel, Ligand-gated ion channel
01
Overview
Cholinergic receptor nicotinic alpha 4 subunit (CHRNA4) encodes the α4 protein, a key subunit of neuronal nicotinic acetylcholine receptors (nAChRs) predominantly found in the brain. The α4 subunit commonly assembles with β2 subunits to form the α4β2 nAChR subtype, which functions as a pentameric ligand-gated ion channel mediating fast synaptic transmission. These receptors are activated by acetylcholine and nicotine, permitting the influx of cations (Na⁺, K⁺, Ca²) that influence neurotransmitter release and a range of physiological processes, including cognition, mood, and arousal. Dysfunction in α4-containing nAChRs is implicated in epilepsy, movement disorders, and nicotine addiction. Therapeutically, this target is modulated by drugs for smoking cessation and neurological disorders.
- Other names
- Neuronal acetylcholine receptor subunit alpha-4nAChRα4Cholinergic receptor, neuronal nicotinic, alpha polypeptide 4Acetylcholine receptor, nicotinic, alpha 4 (neuronal)BFNCEBNEBN1NACHRA4NACRA4
02
Mechanism of action
Agonists (e.g. nicotine) bind at the alpha4-beta2 interface and activate the receptor, leading to channel opening and cation influx Antagonists inhibit receptor activity, blocking synaptic transmission
03
Biological functions
Signal transductionMediation of fast synaptic transmissionRegulation of neurotransmitter releaseModulation of sleep, arousal, attention, anxiety, pain perception, and memoryInvolvement in early brain development
04
Disease associations
Neurodegenerative diseaseEpilepsy (particularly autosomal dominant nocturnal frontal lobe epilepsy)Movement disorders (e.g. paroxysmal kinesogenic dyskinesia)Addiction (nicotine addiction)
05
Safety considerations
Risk of addiction for agonists like nicotinePotential seizures and epilepsy with gain-of-function mutationsCognitive and neuropsychiatric effects associated with dysregulated cholinergic signaling
06
Interacting drugs
Nicotine
5 more in the full profile.
07
Biomarkers
Genetic variants (especially in CHRNA4) act as biomarkers for nocturnal frontal lobe epilepsy and susceptibility to nicotine dependence
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