Neurotherapeutics

, Volume 10, Issue 4, pp 798–807

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

  • Selva Baltan
  • Richard S. Morrison
  • Sean P. Murphy
Review

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.

Keywords

Cerebral ischemia Zn-dependent histone deacetylase infarct mitochondria p53 aging 

Supplementary material

13311_2013_201_MOESM1_ESM.pdf (511 kb)
ESM 1(PDF 510 kb)

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Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2013

Authors and Affiliations

  • Selva Baltan
    • 1
  • Richard S. Morrison
    • 2
  • Sean P. Murphy
    • 2
  1. 1.Department of Neurosciences, Lerner Research InstituteThe Cleveland Clinic FoundationClevelandUSA
  2. 2.Department of Neurological SurgeryUniversity of Washington School of MedicineSeattleUSA

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