Chiappelli_2025_Bioinformation_21_571

The non-neuronal cholinergic system plays an important role in the modulation of immunity and in particular the control of the inflammatory response. The cholinergic anti-inflammatory pathway is mediated principally by the alpha7-nicotinic acetylcholine receptor (alpha7-nAChR) and its receptor-specific chaperone, resistance to inhibitors of cholinesterase (RIC)-3 chaperone protein. The point is made in this writing that therapeutic stimulation of the non-neuronal cholinergic system via, for instance, transcutaneous vagal stimulation, pharmaco-therapeutic activation of alpha7-nAChR/RIC-3, or stimulation of the pathway by other means, including microRNA treatment interventions could down-regulate states of inflammation such as the cytokines storm and chronic systemic inflammation in aging - viz, inflammaging. It is possible and even likely that controlling inflammaging by intervening on the non-neuronal cholinergic system (NNCS) will be beneficial to a wide range of aging-related diseases, from type 2 diabetes and obesity to periodontal disease.