Evaluation of histone deacetylase inhibitors as therapeutics for neurodegenerative diseases

Methods Mol Biol. 2011;793:495-508. doi: 10.1007/978-1-61779-328-8_32.

Abstract

Various neurodegenerative diseases are associated with aberrant gene expression. We recently identified a novel class of pimelic o-aminobenzamide histone deacetylase (HDAC) inhibitors that show promise as therapeutics in the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD). Here, we describe the various techniques used in our laboratories to dissect mechanisms of gene silencing in FRDA and HD, and to test our HDAC inhibitors for their ability to reverse changes in gene expression in cellular models.

MeSH terms

  • Acetylation / drug effects
  • Blotting, Western
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Separation
  • Chromatin / metabolism
  • Chromatin Immunoprecipitation
  • Drug Evaluation, Preclinical / methods*
  • Friedreich Ataxia / drug therapy*
  • Friedreich Ataxia / genetics
  • Friedreich Ataxia / metabolism
  • Gene Expression Regulation / drug effects
  • Gene Silencing / drug effects
  • Histone Deacetylase Inhibitors / pharmacology*
  • Histone Deacetylase Inhibitors / therapeutic use*
  • Histone Deacetylases / metabolism*
  • Histones / metabolism
  • Humans
  • Huntington Disease / drug therapy*
  • Huntington Disease / genetics
  • Huntington Disease / metabolism
  • Iron-Binding Proteins / genetics
  • Iron-Binding Proteins / metabolism
  • Laboratories
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Male
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Chromatin
  • Histone Deacetylase Inhibitors
  • Histones
  • Iron-Binding Proteins
  • RNA, Messenger
  • frataxin
  • Histone Deacetylases