Int Immunopharmacol.2025 Jan 27:146:113939. https://linkinghub.elsevier.com/retrieve/pii/S1567-5769(24)02461-5
Title:The regulatory role of the Netrin-1/UNC5H3 pathway in neuronal pyroptosis after stroke
Abstract
Currently, stroke is a disease with high disability and mortality risks and no effective treatment. The pathogenesis and molecular mechanisms of neuronal damage in stroke are highly complex. Pyroptosis participates in neuronal death after stroke. Thus, inhibiting pyroptosis could be a potential therapeutic method to improve the poor prognosis of stroke patients. However, the regulated mechanisms of pyroptosis remain unclear. Furthermore, although the role of Netrin-1 and its receptors in ischemic apoptosis is well-known, their specific functions in ischemia-induced pyroptosis are still unknown. The current study aimed to explore whether Netrin-1 and its receptor UNC5H3 could regulate pyroptosis after ischemic stroke. PC12 cells decreased Netrin-1 expression and increased UNC5H3 expression after OGD/R injury, subsequently leading to the dissociation of Netrin-1 from UNC5H3, accompanied by increased pyroptotic activity. UNC5H3 inhibition in the absence of Netrin-1 could inhibit OGD/R injury-induced cell pyroptosis. Furthermore, a decreased Netrin-1/UNC5H3 interaction could mitigate Netrin-1-elicited protective role against OGD/R injury. Additionally, Netrin-1 provided a neuroprotective effect against MCAO injury in vivo. Therefore, the Netrin-1/UNC5H3 pathway plays a regulatory role in neuronal pyroptosis after ischemic stroke, representing a novel therapeutic target and strategy for stroke therapy.
Product: DHB70501,NTN1/Netrin-1 (NP137)
