Customer Publication
GSK’872 Improves Prognosis of Traumatic Brain Injury by Switching Receptor-Interacting Serine/Threonine-Protein Kinase 3-dependent Necroptosis to Cysteinyl Aspartate Specific Proteinase-8-Dependent Apoptosis
Journal: World Neurosurgery (2024)
Research Areas: Neuronology
Cell Lines: HT22 (Mouse hippocampal cells)
Summary: The paper presents a significant breakthrough in the understanding and treatment of Traumatic Brain Injury (TBI). The study explores the role of receptor-interacting serine/threonine-protein kinase 3 (RIP3)-mediated necroptosis in TBI. Necroptosis, a form of programmed cell death, has been observed in TBI, but its underlying mechanisms and roles were not well understood. The researchers established a cell-stretching injury and mouse TBI model to evaluate the relationships among necroptosis, apoptosis, inflammation, and TBI. They found that necroptosis mediated by RIP1, RIP3, and mixed lineage kinase domain-like protein (MLKL) was involved in secondary TBI.Interestingly, the inhibition of RIP3 by GSK’872, a specific inhibitor, blocked necroptosis and reduced the activity of Akt/mTOR, leading to the alleviation of inflammation by reducing the levels of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3). Moreover, the inhibition of RIP3 by GSK’872 promoted the activity of cysteinyl aspartate specific proteinase-8 (Caspase-8), an enzyme involved in apoptosis and inflammation1.The results suggest that RIP3 inhibition could improve the prognosis of TBI, based on the attenuation of inflammation by switching RIP3-dependent necroptosis to Caspase-8-dependent apoptosis.HoloMonitor M4 was used to study the cell morphology, includng the cell area and thickness of the injured cells.