MALT1 promotes necroptosis in stroke rat brain via targeting the A20/RIPK3 pathway

Telaprevir Improves Memory and Cognition in Mice Suffering Ischemic Stroke via Targeting MALT1-Mediated Calcium Overload and Necroptosis

“…The activated RIPK3 then phosphorylates and activates a pseudokinase named MLKL that eventually oligomerizes and permeabilizes the plasma membrane for executing necroptosis. − Other labs’ study and ours have consistently demonstrated that necroptosis is a major form of ischemic nerve cell death, and targeting the corresponding signaling pathways could be a potential strategy for protecting against ischemic brain injury. − As the engagement of the RIPK1/RIPK3/MLKL pathway in necroptosis has been well-established, the attention of research interest has recently been turned to the mechanisms in charge of regulating the RIPK1/RIPK3/MLKL pathway. Most recently, we have demonstrated that MALT1 can promote necroptosis in the ischemic stroke brain by degrading A20, which causes a decrease in its ability to deubiquitinate RIPK3 at k63 and in turn activation of the RIPK1/RIPK3/MLKL signaling pathway . This report reminds us that telaprevir perhaps suppresses RIPK1/RIPK3/MLKL-dependent necroptosis in ischemic stroke via inhibition of MALT1.…”

“…Most recently, we have demonstrated that MALT1 can promote necroptosis in the ischemic stroke brain by degrading A20, which causes a decrease in its ability to deubiquitinate RIPK3 at k63 and in turn activation of the RIPK1/RIPK3/MLKL signaling pathway. 11 This report reminds us that telaprevir perhaps suppresses RIPK1/ RIPK3/MLKL-dependent necroptosis in ischemic stroke via inhibition of MALT1. Excitingly, in this study, we really observed significant decreases in the protein levels of RIPK1 and MLKL and a slight decrease in the protein level of RIPK3 along with an obvious reduction in the phosphorylation of RIPK1, RIPK3, and MLKL in the brain of telaprevir-treated stroke mice, further confirming the role of telaprevir in counteracting ischemic stroke injury via inhibition of MALT1.…”

“…Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is an inflammatory regulatory molecule that has been reported to play an important role in a variety of autoimmune diseases and tumors . Interestingly, our recent studies have demonstrated that MALT1 exerted an essential role in ischemic stroke, mainly involving GluN2B activation, Ca 2+ overload, excitotoxicity, and necroptosis. , Therefore, MALT1 might be a novel drug target for the therapy of ischemic stroke. Although several MALT1 inhibitors have been developed, their clinical perspective remains unclear.…”

“…9 Interestingly, our recent studies have demonstrated that MALT1 exerted an essential role in ischemic stroke, mainly involving GluN2B activation, Ca 2+ overload, excitotoxicity, and necroptosis. 10,11 Therefore, MALT1 might be a novel drug target for the therapy of ischemic stroke. Although several MALT1 inhibitors have been developed, their clinical perspective remains unclear.…”