Abraham_2025_Cell.Mol.Neurobiol_45_70

The multifunctional roles of alpha7 nicotinic acetylcholine receptors (alpha7nAChRs), ranging from cognitive enhancement, neuroprotection, and anti-inflammatory action, credit tagging this receptor as "unique" among the cholinergic receptor family. The uniqueness of alpha7nAChRs in neuronal function and communication lies in their high calcium permeability among the cholinergic receptor family. The ionotropic function of alpha7nAChRs is governed by protein kinases' post-translational modification (PTMs), which alter their expression and function, affecting neuronal communication. A decrease in the ionotropic function of alpha7nAChRs and its downstream signaling pathways is observed across many neurologic disorders. The loss of alpha7nAChRs, decreased cholinergic function, and increased acetylcholinesterase levels are commonly associated with neuronal degeneration, cognitive impairment, and decreased memory function. An extensive body of evidence suggests the cognitive benefits of simple nutraceutical supplementation, Vitamin D3 (VD), in many neurologic disorders (Skv et al. in Mol Neurobiol 61:7211-7238, 2024). The present review will, however, focus on recent and past evidence deciphering the unique properties of alpha7nAChRs crucial for brain function. We have also emphasized on the therapeutic benefits of VD supplementation in restoring cholinergic neurotransmission and alpha7nAChRs expression in various neuropsychiatric and neurologic disorders.