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Necrostatin-1: Its Discovery and Application in Cell Death Research

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Necrotic Cell Death

Part of the book series: Cell Death in Biology and Diseases ((CELLDEATH))

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Abstract

Necrostatin-1 (Nec-1) is a small molecule inhibitor of receptor-interacting protein 1 (RIP1) Ser/Thr kinase activity. Initially discovered as an inhibitor of necroptosis, a pathway of programmed necrotic, caspase-independent cell death, Nec-1 has been a valuable tool to investigate the molecular mechanisms of necroptosis. Necroptotic cell death requires the kinase activity of RIP1. RIP1 has well-established roles in mediating NF-κB activation and apoptosis in a kinase-independent manner, but the function of RIP1 kinase has been a focus of recent studies. As a specific inhibitor of RIP1 kinase, Nec-1 has become a critical and widely used tool for defining the function of RIP1 kinase in mediating necroptosis, apoptosis induced in the absence of cIAP1/2, and in the transcription of TNFα. The physiological and pathological roles of necroptosis and RIP1 kinase have also been studied using Nec-1. Inhibition of cellular injury in animal models by Nec-1 has indicated a role for RIP1 kinase after ischemic injury, bacterial and viral infections, as well as other acute injuries such as traumatic brain injury.

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  1. Department of Cell Biology, Harvard Medical School, Boston, MA, USA

    Dana E. Christofferson, Ying Li & Junying Yuan

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  1. Dana E. Christofferson
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  2. Ying Li
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  3. Junying Yuan
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Correspondence to Junying Yuan .

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  1. Department of Physiology, National University of Singapore Yong Loo Lin School of Medicine, Singapore, Singapore

    Han-Ming Shen

  2. Department of Biomedical Molecular Biology (UGent), VIB/University of Ghent Inflammation Research Center (VIB), Zwijnaarde, Belgium

    Peter Vandenabeele

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Christofferson, D.E., Li, Y., Yuan, J. (2014). Necrostatin-1: Its Discovery and Application in Cell Death Research. In: Shen, HM., Vandenabeele, P. (eds) Necrotic Cell Death. Cell Death in Biology and Diseases. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4614-8220-8_16

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