title: Novel protective effects of histone deacetylase inhibition on stroke and white matter ischemic injury.
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.
authors.affiliation: Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH, 44195, USA, baltans@ccf.org.
authors.forename: Selva
authors.initials: S
authors.lastname: Baltan
authors.forename: Richard S
authors.initials: RS
authors.lastname: Morrison
authors.forename: Sean P
authors.initials: SP
authors.lastname: Murphy
mesh_terms: D001369:Axons / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D009413:Nerve Fibers, Myelinated / Q000187:drug effects* / Q000473:pathology; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology
chemical_list: D056572:Histone Deacetylase Inhibitors; D018696:Neuroprotective Agents