Nucleobindin‐2 Derived Multifunctional Peptide Nesfatin‐1: Renoprotective Mechanisms and Therapeutic Promise

Since its discovery in 2006 as an appetite regulator, the nucleobindin-2/nesfatin-1 peptide has emerged as an important regulator of various biological functions. Its role in renal physiology is emerging, with growing evidence suggesting that nesfatin-1 exerts antioxidative, anti-inflammatory, antiapoptotic, and antifibrotic effects in renal tissues by influencing multiple signaling pathways, including PI3K/Akt, NF-κB, MAPK, and Nrf2. These biological actions position nesfatin-1 at the intersection of metabolic regulation and renoprotection. Under pathological conditions, such as high glucose levels, oxidative insults, or chemical-induced nephrotoxicity, nesfatin-1 has demonstrated significant protective effects in both in vitro and in vivo models. Its ability to counteract renal cell injury, reduce pro-inflammatory cytokine expression, and preserve mitochondrial integrity underscores its therapeutic potential. Despite these promising findings, the precise receptor mediating nesfatin-1's actions and its pharmacokinetic profile remain largely unknown, limiting its clinical application. Nevertheless, preclinical studies support its potential as a novel peptide-based therapeutic or biomarker for kidney diseases. This review offers an updated summary on the role of nesfatin-1 in kidney disorders, its underlying mechanism, and future directions. Future studies aimed at the elucidation of its receptor, optimizing delivery strategies, and conducting clinical trials to harness the potential renoprotective properties of nesfatin-1 will pave the way for nesfatin-1-based innovative renal therapy.