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The specific, reversible JNK inhibitor SP600125 improves survivability and attenuates neuronal cell death in experimental cerebral malaria (ECM)

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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.

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Acknowledgments

The authors thank DBT, CSIR, DST, Government of India, New Delhi, and UGC-SAP for financial assistance. S.S.A. and M. M. would like to thank the CSIR for awarding Senior Research Fellowship. The authors greatly acknowledge Miss. Nalini for her technical assistance with confocal microscope.

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Authors and Affiliations

  1. Department of Biotechnology, School of Life Sciences, University of Hyderabad, Gachibowli, Hyderabad, 500 046, India

    Sripada Santosh Anand & Phanithi Prakash Babu

  2. Department of Animal Sciences, School of Life Sciences, University of Hyderabad, Gachibowli, Hyderabad, 500 046, India

    Mulaka Maruthi

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  1. Sripada Santosh Anand
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  2. Mulaka Maruthi
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Correspondence to Phanithi Prakash Babu.

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Anand, S.S., Maruthi, M. & Babu, P.P. The specific, reversible JNK inhibitor SP600125 improves survivability and attenuates neuronal cell death in experimental cerebral malaria (ECM). Parasitol Res 112, 1959–1966 (2013). https://doi.org/10.1007/s00436-013-3352-0

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