title: Targeting histone deacetylases as a multifaceted approach to treat the diverse outcomes of stroke.
abstract: Achieving therapeutic efficacy in ischemic stroke represents one of the biggest challenges in translational neurobiology. Despite extensive efforts, tissue plasminogen activator remains the only available intervention for enhancing functional recovery in humans once a stroke has occurred. To expand the repertoire of therapeutic options in stroke, one must consider and target its diverse pathophysiologies that trigger cell loss in a manner that also permits and enhances neuronal plasticity and repair. Several converging lines of inquiry suggest that histone deacetylase (HDAC) inhibition could be a strategy to achieve these goals. Here, we review evidence that targeting HDACs with low-molecular-weight inhibitors significantly decreases neuronal injury and improves functional outcome in multiple preclinical models of focal ischemia. These salutary effects emanate, in part, from modifications of chromatin and nonchromatin proteins that enhance adaptive gene expression or adaptive protein function. Together, the findings suggest that HDAC inhibition is a strategy capable of targeting diverse pathophysiologies of stroke with a wide therapeutic window.
authors.affiliation: Burke/Cornell Medical Research Institute, 785 Mamaroneck Road, White Plains, NY 10605, USA. bcl2002@med.cornell.edu
authors.forename: Brett
authors.initials: B
authors.lastname: Langley
authors.forename: Camille
authors.initials: C
authors.lastname: Brochier
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rivieccio
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D020521:Stroke / Q000188:drug therapy / Q000201:enzymology*; D016896:Treatment Outcome
chemical_list: D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases