Neuromedin U Signaling Map: Toward Neuropeptide Focused Therapeutic Targets in Cancer and Human Diseases

Neuropeptides play pivotal roles in intercellular communication in the nervous system and peripheral tissues. However, the molecular events underlying their signaling lack a unified representation in the scientific literature. A case in point is Neuromedin U (NMU), a neuropeptide structurally conserved across diverse species with multifaceted roles in integrating metabolic, immune, and stress signaling. Dysregulation of NMU signaling has been correlated to neuronal functions and various metabolic disorders, and is associated with colorectal, breast, and pancreatic cancers. Despite growing interest in NMU as a disease-associated signaling neuropeptide, a comprehensive and standardized schematic representation of its signaling pathway is lacking. We report here a NMU signaling map by systematically curating the literature and classifying NMU signaling events according to known pathway standards. The NMU signaling map included seven activation/inhibition events, 16 enzyme catalysis events, 66 gene regulation events, 30 protein expression events, and 20 translocation events. This NMU signaling map offers a new molecular framework and possibilities for biomarker and drug discovery and development, owing to its relevance in neuronal functions, inflammatory, metabolic, and oncogenic pathways. By consolidating fragmented evidence into a standardized pathway representation, this study serves as a resource for future integrative analyses, hypothesis generation, and translational research toward NMU signaling and neuropeptide-focused therapeutics innovation in cancer and human diseases.