Article ; Online: Histone deacetylase inhibitors as therapeutic agents for acute central nervous system injuries.
Molecular medicine (Cambridge, Mass.)
2011 Volume 17, Issue 5-6, Page(s) 448–456
Abstract: Histone deacetylase (HDAC) inhibitors are emerging as a novel class of potentially therapeutic agents for treating acute injuries of the central nervous system (CNS). In this review, we summarize data regarding the effects of HDAC inhibitor ... ...
| Abstract | Histone deacetylase (HDAC) inhibitors are emerging as a novel class of potentially therapeutic agents for treating acute injuries of the central nervous system (CNS). In this review, we summarize data regarding the effects of HDAC inhibitor administration in models of acute CNS injury and discuss issues warranting clinical trials. We have previously shown that the pan-HDAC inhibitor ITF2357, a compound shown to be safe and effective in humans, improves functional recovery and attenuates tissue damage when administered as late as 24 h after injury. Using a well-characterized, clinically relevant mouse model of closed head injury, we demonstrated that a single dose of ITF2357 administered 24 h after injury improves neurobehavioral recovery and reduces tissue damage. ITF2357-induced functional improvement was found to be sustained up to 14 d after trauma and was associated with augmented histone acetylation. Single postinjury administration of ITF2357 also attenuated injury-induced inflammatory responses, as indicated by reduced glial accumulation and activation as well as enhanced caspase-3 expression within microglia/macrophages after treatment. Because no specific therapeutic intervention is currently available for treating brain trauma patients, the ability to affect functional outcome by postinjury administration of HDAC inhibitors within a clinically feasible timeframe may be of great importance. Furthermore, a growing body of evidence indicates that HDAC inhibitors are beneficial for treating various forms of acute CNS injury including ischemic and hemorrhagic stroke. Because HDAC inhibitors are currently approved for other use, they represent a promising new avenue of treatment, and their use in the setting of CNS injury warrants clinical evaluation. |
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| MeSH term(s) | Animals ; Central Nervous System/drug effects ; Central Nervous System/injuries ; Central Nervous System/pathology ; Histone Deacetylase Inhibitors/therapeutic use ; Humans ; Hydroxamic Acids/therapeutic use ; Mice ; Trauma, Nervous System/drug therapy ; Trauma, Nervous System/metabolism |
| Chemical Substances | Histone Deacetylase Inhibitors ; Hydroxamic Acids ; givinostat hydrochloride (Z02132R2QQ) |
| Language | English |
| Publishing date | 2011-01-25 |
| Publishing country | England |
| Document type | Journal Article ; Review |
| ZDB-ID | 1283676-x |
| ISSN | 1528-3658 ; 1076-1551 |
| ISSN (online) | 1528-3658 |
| ISSN | 1076-1551 |
| DOI | 10.2119/molmed.2011.00038 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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