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  • Perspective
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Emerging mechanisms of disrupted cellular signaling in brain ischemia

Nature Neuroscience volume 14, pages 1369–1373 (2011)Cite this article

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Abstract

Recent findings have provided insights into pathogenic mechanism(s) that may complement and add to the traditional glutamatergic mechanisms to which ischemic brain injury is ascribed. The discovery of mechanisms leading to ionic imbalance and signaling cascades that mediate cross-talk between redundant pathways of cell death, as well as mechanisms that operate downstream of, upstream of and in parallel with excitotoxicity, has spurred new research into therapeutics ranging from proof of concept in animals to human clinical trials. This Perspective presents an integrated consideration of new molecular pathogenic mechanisms underlying ischemic damage in the brain, and how our combined knowledge of these mechanisms and our existing knowledge of excitotoxicity may establish new targets for therapy, by allowing clearer boundaries on what might be expected of a given intervention, and may yield advances that will benefit patients.

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Figure 1: Strategy of perturbing protein-protein interactions involving the postsynaptic scaffolding protein PSD-95.
Figure 2: Possible involvement of NMDARs, TRPM2 and TRPM7 channels in anoxic neuronal death.

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Authors and Affiliations

  1. Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada

    Michael Tymianski

  2. Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada

    Michael Tymianski

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Correspondence to Michael Tymianski.

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M.T. is president and chief executive officer of NoNO Inc., a biotechnology company dedicated to the translation of new therapies discovered in the author's and collaborators' academic laboratories to human clinical trials.

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Tymianski, M. Emerging mechanisms of disrupted cellular signaling in brain ischemia. Nat Neurosci 14, 1369–1373 (2011). https://doi.org/10.1038/nn.2951

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