title: Potential therapeutic approaches for Angelman syndrome.
abstract: BACKGROUND
  Angelman syndrome (AS) is a neurodevelopmental disorder caused by deficiency of maternally inherited UBE3A, an ubiquitin E3 ligase. Despite recent progress in understanding the mechanism underlying UBE3A imprinting, there is no effective treatment. Further investigation of the roles played by UBE3A in the central nervous system (CNS) is needed for developing effective therapies.
  
  
  METHODS
  This review covers the literature related to genetic classifications of AS, recent discoveries regarding the regulation of UBE3A imprinting, alterations in cell signaling in various brain regions and potential therapeutic approaches. Since a large proportion of AS patients exhibit comorbid autism spectrum disorder (ASD), potential common molecular bases are discussed.
  
  
  CONCLUSIONS
  Advances in understanding UBE3A imprinting provide a unique opportunity to induce paternal UBE3A expression, thus targeting the syndrome at its 'root.' However, such efforts have yielded less-than-expected rescue effects in AS mouse models, raising the concern that activation of paternal UBE3A after a critical period cannot correct all the CNS defects that developed in a UBE3A-deficient environment. On the other hand, targeting abnormal downstream cell signaling pathways has provided promising rescue effects in preclinical research. Thus, combined reinstatement of paternal UBE3A expression with targeting abnormal signaling pathways should provide better therapeutic effects.
authors.affiliation: a Department of Basic Medical Sciences, COMP , Western University of Health Sciences , Pomona , CA , USA.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Bi
authors.affiliation: a Department of Basic Medical Sciences, COMP , Western University of Health Sciences , Pomona , CA , USA.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Sun
authors.affiliation: a Department of Basic Medical Sciences, COMP , Western University of Health Sciences , Pomona , CA , USA.
authors.forename: Angela X
authors.initials: AX
authors.lastname: Ji
authors.affiliation: b Graduate College of Biomedical Sciences , Western University of Health Sciences , Pomona , CA , USA.
authors.forename: Michel
authors.initials: M
authors.lastname: Baudry
mesh_terms: D017204:Angelman Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D000818:Animals; D006801:Humans; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases
keywords: Angelman syndrome; Arc; SK2 channel; UBE3A; imprinting; learning and memory; mTor; motor function; synaptic plasticity; ubiquitination