Therapeutic Effect of a Synthetic RORα/γ Agonist in an Animal Model of Autism

Yongjun Wang, Cyrielle Billon, John K. Walker, Thomas P. Burris

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Autism is a developmental disorder of the nervous system associated with impaired social communication and interactions as well excessive repetitive behaviors. There are no drug therapies that directly target the pathology of this disease. The retinoic acid receptor-related orphan receptor α (RORα) is a nuclear receptor that has been demonstrated to have reduced expression in many individuals with autism spectrum disorder (ASD). Several genes that have been shown to be downregulated in individuals with ASD have also been identified as putative RORα target genes. Utilizing a synthetic RORα/γ agonist, SR1078, that we identified previously, we demonstrate that treatment of BTBR mice (a model of autism) with SR1078 results in reduced repetitive behavior. Furthermore, these mice display increased expression of ASD-associated RORα target genes in both the brains of the BTBR mice and in a human neuroblastoma cell line treated with SR1078. These data suggest that pharmacological activation of RORα may be a method for treatment of autism.

Original languageEnglish (US)
Pages (from-to)143-148
Number of pages6
JournalACS Chemical Neuroscience
Volume7
Issue number2
DOIs
Publication statusPublished - Feb 17 2016

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Keywords

  • Autism
  • behavior
  • drug discovery
  • nuclear receptor
  • orphan receptor

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology

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