High levels of nitric oxide and peroxynitrite with protein nitration: a new therapeutic target for gliomas

The gap junction signaling pathway is a core hub mediating intercellular communication, which plays a vital role in maintaining tissue homeostasis, and its dysfunction is closely related to glioma. Nitroproteomics studies have shown that protein tyrosine nitration plays an important role in the progression of glioma, and gap junction is one of the significantly enriched nitroprotein signaling pathways in glioma; proteoformics reveals that nitration can produce various proteoforms of related proteins, which have different functional states in different subtypes of glioma, suggesting that nitration may alter the functional states of related proteins in gap junction pathways. When levels of nitric oxide and peroxynitrite (ONOO-) rise, they induce the tyrosine nitration of key proteins in the gap junction pathway; this nitration not only interferes with the function of the gap junction pathway, but also affects other gap junction-linked signaling networks. Forming an attack network on the gap junction pathway through multi-pathway cross-regulation has great potential for therapeutic strategies targeting the gap junction pathway. We recommend in-depth studies of the gap junction signaling pathway and potential drugs targeting gap junction signals, including drugs that target gap junction communication activators, nitration inhibitors, and drugs that directly target specific nitroproteins, combined with conventional chemotherapy or immune checkpoint inhibitors, as well as the construction of personalized medical frameworks as important future research directions.