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TR(I)Pping towards treatment for ischemia

Nature Neuroscience volume 12, pages 1215–1216 (2009)Cite this article

A study in this issue found that suppressing expression of TRPM7 in hippocampal CA1 neurons conferred resistance to ischemic cell death, preserved cell function and prevented ischemia-induced deficits in memory.

Stroke is the third leading cause of death in the US and is a leading cause of disability. Despite substantial progress in delineating the multiple ischemia-induced molecular cascades that contribute to neuronal death, there are still no effective stroke treatments. The contribution of excitotoxicity, mediated by glutamatergic NMDA receptors, to ischemia-induced cell death is well appreciated. However, because these receptors are widely expressed and are important for diverse neuronal functions, it is not surprising that blocking these receptors with antagonists is not well tolerated, especially in confused, elderly stroke patients. Moreover, the efficacy of NMDA receptor antagonists is restricted to a very short time window following the onset of ischemia. The discovery and subsequent targeting of mechanisms with better tolerability and longer treatment windows are desperately needed for the effective treatment of stroke. A study in this issue shows that inhibiting transient receptor potential melastatin 7 (TRPM7) channel function may fulfill this need. Using viral delivery of small hairpin RNA (shRNA) to knockdown TRPM7 channels in CA1 pyramidal neurons, Sun et al.1 found that reduced TRPM7 channel expression greatly diminishes pyramidal cell death after global ischemia, maintaining normal CA1 neuronal function and hippocampal-dependent behaviors.

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Figure 1: The expression and activation mechanisms of TRPM channels.

References

  1. Sun, H.-S. et al. Nat. Neurosci. 12, 1300–1307 (2009).

    CAS  Article  Google Scholar 

  2. Nilius, B. & Voets, T. Pflugers Arch. 451, 1–10 (2005).

    CAS  Article  Google Scholar 

  3. Aarts, M. et al. Cell 115, 863–877 (2003).

    CAS  Article  Google Scholar 

  4. Oancea, E., Wolfe, J.T. & Clapham, D.E. Circ. Res. 98, 245–253 (2006).

    CAS  Article  Google Scholar 

  5. Reading, S.A. & Brayden, J.E. Stroke 38, 2322–2328 (2007).

    CAS  Article  Google Scholar 

  6. Gerzanich, V. et al. Nat. Med. 15, 185–191 (2009).

    CAS  Article  Google Scholar 

  7. Krapivinsky, G. et al. Neuron 52, 485–496 (2006).

    CAS  Article  Google Scholar 

  8. Jin, J. et al. Science 322, 756–760 (2008).

    CAS  Article  Google Scholar 

  9. Schmitz, C. et al. Cell 114, 191–200 (2003).

    CAS  Article  Google Scholar 

  10. McNulty, S. & Fonfria, E. Pflugers Arch. 451, 235–242 (2005).

    CAS  Article  Google Scholar 

  11. Fonfria, E. et al. J. Neurochem. 95, 715–723 (2005).

    CAS  Article  Google Scholar 

  12. Olah, M.E. et al. J. Physiol. (Lond.) 587, 965–979 (2009).

    CAS  Article  Google Scholar 

  13. Kraft, R. et al. Am. J. Physiol. Cell Physiol. 286, C129–C137 (2004).

    CAS  Article  Google Scholar 

  14. Bond, C.E. & Greenfield, S.A. Glia 55, 1348–1361 (2007).

    Article  Google Scholar 

  15. Besancon, E. et al. Trends Pharmacol. Sci. 29, 268–275 (2008).

    CAS  Article  Google Scholar 

Download references

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  1. David A. Rempe is in the Department of Neurology, and Takahiro Takano and Maiken Nedergaard are in the Department of Neurosurgery, University of Rochester, Rochester, New York, USA. maiken_nedergaard@urmc.rochester.edu or david_rempe@urmc.rochester.edu,

    David A Rempe, Takahiro Takano & Maiken Nedergaard

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  1. David A Rempe
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  2. Takahiro Takano
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  3. Maiken Nedergaard
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Rempe, D., Takano, T. & Nedergaard, M. TR(I)Pping towards treatment for ischemia. Nat Neurosci 12, 1215–1216 (2009). https://doi.org/10.1038/nn1009-1215

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