Neurodevelopmental disorders: Unsilencing dormant Ube3a—hope for Angelman syndrome?

  title={Neurodevelopmental disorders: Unsilencing dormant Ube3a—hope for Angelman syndrome?},
  author={Katy H. Malpass},
  journal={Nature Reviews Neurology},
  • K. Malpass
  • Published 24 January 2012
  • Medicine
  • Nature Reviews Neurology
Angelman syndrome (AS) is a neurodevelopmental disorder caused by mutation or deletion of the gene that encodes ubiquitin protein ligase E3A (UBE3A). In a new study, researchers from the University of North Carolina, NC, USA have found that topoisomerase inhibitors can induce transcription of a silent, functional allele of Ube3a in mice. Exploration into how these compounds unsilence this gene might provide insight into the mechanism of disease, and could lead to the development of therapies… 
Emerging Gene and Small Molecule Therapies for the Neurodevelopmental Disorder Angelman Syndrome
Angelman syndrome is reviewed and how loss-of-function of the maternal UBE3A contributes to the disorder and how small molecule drugs and gene therapies offer a promising approach for the treatment of the disorder.
Simvastatin Restores HDAC1/2 Activity and Improves Behavioral Deficits in Angelman Syndrome Model Mouse
It is demonstrated that the treatment of simvastatin to primary cortical neuronal culture prepared from AS mice embryo also rescues altered acetylation of histones H3 and H4 and the level of BDNF.


Topoisomerase inhibitors unsilence the dormant allele of Ube3a in neurons
Paternal expression of Ube3a remained elevated in a subset of spinal cord neurons for at least 12 weeks after cessation of topotecan treatment, indicating that transient topoisomerase inhibition can have enduring effects on gene expression.