The neurokinin 1 receptor with the natural substrate substance P is one of the intensely studied receptors among the neurokinin receptors. The intracellular signaling mechanism uses G protein-coupled transduction regulating various physiological processes from nausea to Alzheimer's disease. The neurokinin 1 receptor plays a significant role in neuroinflammation-mediated alterations in neural circuitry. Neurokinin 1 receptor antagonists are selective, potent and exhibited efficacy in animal models of nervous system disorders. Evolving data now strengthen the viewpoint of brain substance P/neurokinin 1 receptor axis-mediated action in neural circuit dysfunction. Thus, a deep-rooted analysis of disease mechanism in which the neurokinin 1 receptor is involved is necessary for augmenting disease models which encourage the pharmaceutical industry to intensify the research pipeline. This review is an attempt to outline the concept of neurokinin 1 receptor signaling interlinked to the brain innate immune system. We also uncover the mechanisms of the neurokinin 1 receptor involved in neurological disorder and various methods of modulating the neurokinin 1 receptor, which may result in therapeutic action.
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