α7 nicotinic acetylcholine receptor and depression: Mechanistic insights and therapeutic prospects.

Depression is a highly prevalent and disabling psychiatric disorder worldwide, yet current treatments are limited by delayed onset and suboptimal response rates. The α7 nicotinic acetylcholine receptor (α7 nAChR), a ligand-gated cation channel within the central cholinergic system, is highly expressed in emotion-regulating regions including the hippocampus and prefrontal cortex, where it modulates neurotransmitter release, synaptic plasticity, and neuroinflammation. Accumulating preclinical evidence indicates that α7 nAChR activation may exert antidepressant-like effects by modulating monoaminergic neurotransmission, enhancing brain-derived neurotrophic factor (BDNF) expression, attenuating microglial activation and proinflammatory cytokine release, and engaging gut-brain-axis pathways. Nevertheless, heterogeneous findings, target-engagement hurdles, and a paucity of adequately powered clinical studies have limited translation to the clinic. This review systematically summarizes the structural features, mechanistic insights, and therapeutic advances of α7 nAChR in depression, with the aim of providing a theoretical basis and future directions for targeted interventions and novel drug discovery.