Methamphetamine exposure induces neuronal programmed necrosis by activating the receptor-interacting protein kinase 3 -related signalling pathway.
Xu ZhaoJiancong LuXuebing ChenZhengxiang GaoCui ZhangChuanxiang ChenDongfang QiaoHuijun WangPublished in: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (2021)
Methamphetamine (METH) is a synthetic drug with severe neurotoxicity, however, the regulation of METH-induced neuronal programmed necrosis remains poorly understood. The aim of this study was to identify the molecular mechanisms of METH-induced neuronal programmed necrosis. We found that neuronal programmed necrosis occurred in the striatum of brain samples from human and mice that were exposed to METH. The receptor-interacting protein kinase 3 (RIP3) was highly expressed in the neurons of human and mice exposed to METH, and RIP3-silenced or RIP1-inhibited protected neurons developed neuronal programmed necrosis in vitro and in vivo following METH exposure. Moreover, the RIP1-RIP3 complex causes cell programmed necrosis by regulating mixed lineage kinase domain-like protein (MLKL)-mediated cell membrane rupture and dynamin-related protein 1 (Drp1)-mediated mitochondrial fission. Together, these data indicate that RIP3 plays an indispensable role in the mechanism of METH-induced neuronal programmed necrosis, which may represent a potential therapeutic target for METH-induced neurotoxicity.
Keyphrases
- protein kinase
- high glucose
- endothelial cells
- diabetic rats
- cerebral ischemia
- drug induced
- oxidative stress
- type diabetes
- emergency department
- single cell
- signaling pathway
- stem cells
- machine learning
- cell therapy
- risk assessment
- early onset
- metabolic syndrome
- white matter
- bone marrow
- electronic health record
- climate change
- induced pluripotent stem cells
- binding protein
- insulin resistance
- high fat diet induced