Putting the 'HAT' back on survival signalling: The promises and challenges of HDAC inhibition in the treatment of neurological conditions

Sama F. Sleiman, Manuela Basso, Lata Mahishi, Alan P. Kozikowski, Mary E. Donohoe, Brett Langley, Rajiv R. Ratan

Research output: Contribution to journalReview article

Abstract

Decreased histone acetyltransferase activity and transcriptional dysfunction have been implicated in almost all neurodegenerative conditions. Increasing net histone acetyltransferase activity through inhibition of the histone deacetylases (HDACs) has been shown to be an effective strategy to delay or halt progression of neurological disease in cellular and rodent models. These findings have provided firm rationale for Phase I and Phase II clinical trials of HDAC inhibitors in Huntington's disease, spinal muscular atrophy, and Freidreich's ataxia. In this review, we discuss the current findings and promise of HDAC inhibition as a strategy for treating neurological disorders. Despite the fact that HDAC inhibitors are in an advanced stage of development, we suggest other approaches to modulating HDAC function that may be less toxic and more efficacious than the canonical agents developed so far.

Original languageEnglish (US)
Pages (from-to)573-584
Number of pages12
JournalExpert Opinion on Investigational Drugs
Volume18
Issue number5
DOIs
StatePublished - May 1 2009

Keywords

  • Histone deacetylase inhibitors
  • Histone deacetylases
  • Neurodegeneration
  • Therapeutics
  • Transcription

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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