Hydroxamate-based histone deacetylase inhibitors can protect neurons from oxidative stress via a histone deacetylase-independent catalase-like mechanism Academic Article uri icon


MeSH Major

  • Histone Deacetylase Inhibitors
  • Histone Deacetylases
  • Hydroxamic Acids
  • Neurons


  • Histone deacetylase (HDAC) inhibitors have shown enormous promise for treating various disease states, presumably due to their ability to modulate acetylation of histone and non-histone proteins. Many of these inhibitors contain functional groups capable of strongly chelating metal ions. We demonstrate that several members of one such class of compounds, the hydroxamate-based HDAC inhibitors, can protect neurons from oxidative stress via an HDAC-independent mechanism. This previously unappreciated antioxidant mechanism involves the in situ formation of hydroxamate-iron complexes that catalyze the decomposition of hydrogen peroxide in a manner reminiscent of catalase. We demonstrate that while many hydroxamate-containing HDAC inhibitors display a propensity for binding iron, only a subset form active catalase mimetics capable of protecting neurons from exogenous H2O2. In addition to their impact on stroke and neurodegenerative disease research, these results highlight the possibility that HDAC-independent factors might play a role in the therapeutic effects of hydroxamate-based HDAC inhibitors.

publication date

  • April 23, 2015



  • Academic Article



  • eng

PubMed Central ID

  • PMC4562013

Digital Object Identifier (DOI)

  • 10.1016/j.chembiol.2015.03.014

PubMed ID

  • 25892200

Additional Document Info

start page

  • 439

end page

  • 45


  • 22


  • 4