The network map of nesfatin-1-mediated signaling pathway in physiological regulation and pathological conditions

Nesfatin-1 is a peptide hormone derived from the precursor protein Nucleobindin-2 (NUCB2) and was discovered recently in the rat hypothalamus. Nesfatin-1 is primarily expressed in the brain, particularly in the hypothalamus. It regulates food intake, body weight, gastrointestinal and cardiovascular functions, cell proliferation, protection against neurotoxicity, and energy homeostasis. Nesfatin-1 acts through an unidentified GPCR, activating key downstream signaling cascades such as MAPKs, JAK/STAT, and PI3K/AKT. The significance of Nesfatin-1 in various physiological processes and pathological conditions made us develop an ideal signaling pathway map. Using NetPath annotation criteria, following a biocuration process, we gathered experimentally derived pathway information from the scientific literature downloaded from PubMed, enabling it to be viewed as a single pathway map. The manual curation of chosen articles resulted in a total of 100 molecules grouped into 20 activation/inhibition, 14 enzyme-catalysis, 42 gene regulations, 61 protein regulations, and two translocation events. Proteins linked to adenocarcinoma in our pathway map were cross-referenced with pathway databases to find unannotated proteins, revealing annotation gaps. The highly curated Nesfatin-1–mediated signaling pathway is expected to facilitate biomedical research by enabling insights into the roles of Nesfatin-1 regulated molecules by Nesfatin-1 under diverse physiological and pathological conditions.