Methamphetamine exposure induces neuronal programmed necrosis by activating the receptor‐interacting protein kinase 3 ‐related signalling pathway

Methamphetamine (METH) is a synthetic drug with severe neurotoxicity, however, the regulation of METH-induced neuronal programmed necrosis remains poorly understood. The aim this study was to identify molecular mechanisms necrosis. We found that occurred in striatum brain samples from human and mice were exposed METH. receptor-interacting protein kinase 3 (RIP3) highly expressed neurons METH, RIP3-silenced or RIP1-inhibited protected developed vitro vivo following METH exposure. Moreover, RIP1-RIP3 complex causes cell by regulating mixed lineage domain-like (MLKL)-mediated membrane rupture dynamin-related 1 (Drp1)-mediated mitochondrial fission. Together, these data indicate RIP3 plays an indispensable role mechanism necrosis, which may represent potential therapeutic target for neurotoxicity.