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

Selva Baltan, Richard S. Morrison, Sean P. Murphy

Research output: Contribution to journalReview articlepeer-review

30 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)798-807
Number of pages10
JournalNeurotherapeutics
Volume10
Issue number4
DOIs
StatePublished - Oct 2013
Externally publishedYes

Keywords

  • aging
  • Cerebral ischemia
  • infarct
  • mitochondria
  • p53
  • Zn-dependent histone deacetylase

ASJC Scopus subject areas

  • Pharmacology
  • Clinical Neurology
  • Pharmacology (medical)

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