Tacr3/NK3R: Beyond Their Roles in Reproduction

The Tacr3 gene encodes tachykinin receptor 3 (NK3R), which belongs to the tachykinin receptor family. This family of proteins includes typical G protein-coupled receptors and belongs to the rhodopsin subfamily. NK3R functions by binding to its high-affinity ligand, neurokinin B(NKB). The role of Tacr3/NK3R in growth and reproduction has been extensively studied, but Tacr3/NK3R is also widely expressed in the nervous system from the spinal cord to the brain and is involved in both physiological and pathological processes in the nervous system, including mood disorders, chronic pain, learning and memory deficiencies, Alzheimer's disease, Parkinson's disease, addiction-related processes, hypoxic-ischemic encephalopathy, body fluid management, neural development, and schizophrenia. Here, we summarize the structure of NK3R/NKB and its cellular signaling as well as the expression of Tacr3/NK3R in the nervous system, and we provide a comprehensive summary of the role of Tacr3/NK3R in neurological diseases, including reproduction-related disorders and other neurological diseases. At the end of this review, we propose the hypothesis that Tacr3/NK3R mediates a variety of brain functions by affecting the excitability of different neurons with specific functions. On the basis of this "excited or not" hypothesis, more studies related to Tacr3 should be carried out in other nervous system diseases in order to better understand the biological roles of Tacr3.