Differential histone deacetylase mRNA expression patterns in amyotrophic lateral sclerosis

J Neuropathol Exp Neurol. 2010 Jun;69(6):573-81. doi: 10.1097/NEN.0b013e3181ddd404.


Histone deacetylases (HDACs) are important regulators of gene expression and cell differentiation. The HDAC inhibitors have recently been considered as potential novel neuroprotective drugs for the treatment of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). A major limitation, however, lies in the broad spectrum of action of currently available HDAC inhibitors that may cause a variety of toxic side effects. The mRNA expression levels of the HDAC isoforms HDACs 1 to 11 have previously been characterized in rat brain but have not been studied in human tissue. Using in situ hybridization histochemistry and immunohistochemistry we assessed the distribution and expression levels of HDACs 1to 11 in postmortem ALS and control brain and spinal cord specimens (n = 6 cases each) to determine alterations in the mRNA expression pattern that could provide a basis for disease-specific therapies. We found a reduction of HDAC 11 mRNA and increased HDAC 2 levels in ALS brain and spinal cord compared with controls. A more precise knowledge of the disease-related expression pattern could lead to the development of more specific pharmacotherapeutic approaches.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amyotrophic Lateral Sclerosis / genetics*
  • Amyotrophic Lateral Sclerosis / metabolism
  • Brain / metabolism*
  • Case-Control Studies
  • Female
  • Gene Expression / genetics
  • Histone Deacetylases / genetics*
  • Histone Deacetylases / metabolism
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Male
  • Middle Aged
  • Neurons / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Spinal Cord / metabolism*


  • RNA, Messenger
  • Histone Deacetylases