title: The specific, reversible JNK inhibitor SP600125 improves survivability and attenuates neuronal cell death in experimental cerebral malaria (ECM).
abstract: Cerebral malaria (CM) is the most severe complication of Plasmodium falciparum in humans and major cause of death. SP600125 is a specific, small molecule inhibitor of JNK that prevents the phosphorylation of c-Jun and blocks the expression of proinflammatory cytokines and attenuates neuronal apoptosis in several neurodegenerative disorders. We evaluated the effect of SP600125 treatment on the survival of Plasmodium berghei ANKA (PbA)-infected C57BL/6J mice. Administration of SP600125 improved survival in PbA-infected C57BL6J mice but has no effect on parasitemia. Further, SP600125 administration resulted in attenuation of neuronal cell death along with inhibition of proinflammatory mediators TNF-α and COX-2 and proapoptotic mediators p-c-Jun and active caspase 3 in PbA-infected mice. The promising findings of this study make SP600125 a potential agent for supportive therapy to alleviate inflammation and neuronal cell death associated with CM.
authors: Department of Biotechnology, School of Life Sciences, University of Hyderabad, Gachibowli, Hyderabad, 500 046, India.
authors: Sripada Santosh
authors: SS
authors: Anand
authors: Mulaka
authors: M
authors: Maruthi
authors: Phanithi Prakash
authors: PP
authors: Babu
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000008:administration & dosage* / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000188:drug therapy; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors*; D016779:Malaria, Cerebral / Q000150:complications / Q000188:drug therapy* / Q000401:mortality* / Q000469:parasitology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects*; D010962:Plasmodium berghei / Q000187:drug effects*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000873:Anthracenes; D004791:Enzyme Inhibitors; C432165:pyrazolanthrone; D048670:MAP Kinase Kinase 4