Transcriptional therapy with the histone deacetylase inhibitor trichostatin A ameliorates experimental autoimmune encephalomyelitis. Academic Article uri icon

Overview

abstract

  • We demonstrate that the histone deacetylase (HDAC) inhibitor drug trichostatin A (TSA) reduces spinal cord inflammation, demyelination, neuronal and axonal loss and ameliorates disability in the relapsing phase of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). TSA up-regulates antioxidant, anti-excitotoxicity and pro-neuronal growth and differentiation mRNAs. TSA also inhibits caspase activation and down-regulates gene targets of the pro-apoptotic E2F transcription factor pathway. In splenocytes, TSA reduces chemotactic, pro-Th1 and pro-proliferative mRNAs. A transcriptional imbalance in MS may contribute to immune dysregulation and neurodegeneration, and we identify HDAC inhibition as a transcriptional intervention to ameliorate this imbalance.

publication date

  • July 1, 2005

Research

keywords

  • Encephalomyelitis, Autoimmune, Experimental
  • Gene Expression Regulation
  • Hydroxamic Acids
  • Protein Synthesis Inhibitors

Identity

Scopus Document Identifier

  • 20444446595

Digital Object Identifier (DOI)

  • 10.1016/j.jneuroim.2005.02.022

PubMed ID

  • 15885809

Additional Document Info

volume

  • 164

issue

  • 1-2