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Novel Protective Effects of Histone Deacetylase Inhibition on Stroke and White Matter Ischemic Injury

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Neurotherapeutics

Abstract

Understanding how epigenetics influences the process and progress of a stroke could yield new targets and therapeutics for use in the clinic. Experimental evidence suggests that inhibitors of zinc-dependent histone deacetylases can protect neurons, axons, and associated glia from the devastating effects of oxygen and glucose deprivation. While the specific enzymes involved have yet to be clearly identified, there are hints from somewhat selective chemical inhibitors and also from the use of specific small hairpin RNAs to transiently knockdown protein expression. Neuroprotective mechanisms implicated thus far include the upregulation of extracellular glutamate clearance, inhibition of p53-mediated cell death, and maintenance of mitochondrial integrity. The histone deacetylases have distinct cellular and subcellular localizations, and discrete substrates. As a number of chemical inhibitors are already in clinical use for the treatment of cancer, repurposing for the stroke clinic should be expedited.

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Acknowledgments

We thank past and present members of our laboratories for their many contributions. Continuing grant funding is from NIH-NIA/NINDS, American Heart Association, and American Stroke Association. The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH, 44195, USA

    Selva Baltan

  2. Department of Neurological Surgery, University of Washington School of Medicine, Seattle, WA, USA

    Richard S. Morrison & Sean P. Murphy

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  1. Selva Baltan
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Correspondence to Selva Baltan.

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Baltan, S., Morrison, R.S. & Murphy, S.P. Novel Protective Effects of Histone Deacetylase Inhibition on Stroke and White Matter Ischemic Injury. Neurotherapeutics 10, 798–807 (2013). https://doi.org/10.1007/s13311-013-0201-x

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