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Potential therapeutic approaches for Angelman syndrome
- Source :
- Expert Opinion on Therapeutic Targets. 20:601-613
- Publication Year :
- 2015
- Publisher :
- Informa Healthcare, 2015.
-
Abstract
- 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.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.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.
- Subjects :
- 0301 basic medicine
congenital, hereditary, and neonatal diseases and abnormalities
Ubiquitin-Protein Ligases
Clinical Biochemistry
Epigenetics of autism
Article
03 medical and health sciences
0302 clinical medicine
Neurodevelopmental disorder
Angelman syndrome
Drug Discovery
UBE3A
medicine
Animals
Humans
Effective treatment
Imprinting (psychology)
Pharmacology
Genetics
biology
medicine.disease
Ubiquitin ligase
030104 developmental biology
Autism spectrum disorder
biology.protein
Molecular Medicine
Angelman Syndrome
Neuroscience
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 17447631 and 14728222
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- Expert Opinion on Therapeutic Targets
- Accession number :
- edsair.doi.dedup.....2ea27a7f7a4b3da7458ddb4b40783034