{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAlpha7 nicotinic acetylcholine receptors (α7 nAChRs) serve as pivotal mediators in the neural regulation of inflammation. In multiple models of sepsis, endotoxemia, and acute organ injury, activation of α7 nAChRs—whether via endogenous acetylcholine released from vagal efferents or through exogenous agonists such as choline, nicotine, or specific compounds—suppresses macrophage release of pro‐inflammatory cytokines (for example, tumor necrosis factor, HMGB1, and chemokines). These receptors initiate intracellular signaling cascades including Jak2–STAT3 activation and NF‑κB inhibition that rapidly blunt the systemic inflammatory response, thereby protecting against tissue injury in organs such as the lung, kidney, and gut."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond modulating immune responses, α7 nAChRs also play critical roles in neuroprotection and neuronal signal transduction. Expressed both at the plasma membrane and within mitochondria, these receptors regulate presynaptic neurotransmitter release and postsynaptic excitability, influence synaptic plasticity, and mediate the neuroprotective effects by attenuating pro-apoptotic events (for example, by reducing cytochrome c release and stabilizing intracellular calcium levels). Their activation contributes to improved cognitive performance, mitigated oxidative stress, and preservation of synaptic integrity in models of neurodegeneration, while also modulating pain-related signaling and behavioral outcomes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its roles in immunomodulation and neuroprotection, α7 nAChR signaling exerts multifaceted influences on cellular functions across diverse systems. It fine‑tunes the activity of immune cells—including T lymphocytes and regulatory T cells—to maintain immune homeostasis, modulates nociceptive pathways in chronic inflammatory and neuropathic pain states, and regulates tissue remodeling in epithelial structures such as the airway. 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