FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2016365513> ?p ?o ?g. }

• W2016365513 endingPage "189" @default.
• W2016365513 startingPage "185" @default.
• W2016365513 abstract "Angelman syndrome is a severe neurodevelopmental disorder caused by deletion or mutation of the maternal allele of the ubiquitin protein ligase E3A (UBE3A). In neurons, the paternal allele of UBE3A is intact but epigenetically silenced, raising the possibility that Angelman syndrome could be treated by activating this silenced allele to restore functional UBE3A protein. Using an unbiased, high-content screen in primary cortical neurons from mice, we identify twelve topoisomerase I inhibitors and four topoisomerase II inhibitors that unsilence the paternal Ube3a allele. These drugs included topotecan, irinotecan, etoposide and dexrazoxane (ICRF-187). At nanomolar concentrations, topotecan upregulated catalytically active UBE3A in neurons from maternal Ube3a-null mice. Topotecan concomitantly downregulated expression of the Ube3a antisense transcript that overlaps the paternal copy of Ube3a. These results indicate that topotecan unsilences Ube3a in cis by reducing transcription of an imprinted antisense RNA. When administered in vivo, topotecan unsilenced the paternal Ube3a allele in several regions of the nervous system, including neurons in the hippocampus, neocortex, striatum, cerebellum and spinal cord. 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. Although potential off-target effects remain to be investigated, our findings suggest a therapeutic strategy for reactivating the functional but dormant allele of Ube3a in patients with Angelman syndrome." @default.
• W2016365513 created "2016-06-24" @default.
• W2016365513 creator A5007856961 @default.
• W2016365513 creator A5008853854 @default.
• W2016365513 creator A5011859731 @default.
• W2016365513 creator A5014356370 @default.
• W2016365513 creator A5035411478 @default.
• W2016365513 creator A5038592699 @default.
• W2016365513 creator A5047407682 @default.
• W2016365513 creator A5047547845 @default.
• W2016365513 creator A5051099055 @default.
• W2016365513 creator A5051539758 @default.
• W2016365513 creator A5055678278 @default.
• W2016365513 creator A5063796166 @default.
• W2016365513 creator A5069150872 @default.
• W2016365513 creator A5072548895 @default.
• W2016365513 creator A5078210617 @default.
• W2016365513 date "2011-12-21" @default.
• W2016365513 modified "2023-10-12" @default.
• W2016365513 title "Topoisomerase inhibitors unsilence the dormant allele of Ube3a in neurons" @default.
• W2016365513 cites W1540457577 @default.
• W2016365513 cites W1543569607 @default.
• W2016365513 cites W1973485468 @default.
• W2016365513 cites W1983532821 @default.
• W2016365513 cites W1985513877 @default.
• W2016365513 cites W1992577657 @default.
• W2016365513 cites W1995783954 @default.
• W2016365513 cites W1997361520 @default.
• W2016365513 cites W2007227912 @default.
• W2016365513 cites W2008044453 @default.
• W2016365513 cites W2016315625 @default.
• W2016365513 cites W2016577628 @default.
• W2016365513 cites W2017107955 @default.
• W2016365513 cites W2020715648 @default.
• W2016365513 cites W2024386053 @default.
• W2016365513 cites W2030282106 @default.
• W2016365513 cites W2031123443 @default.
• W2016365513 cites W2037586865 @default.
• W2016365513 cites W2045819396 @default.
• W2016365513 cites W2069717852 @default.
• W2016365513 cites W2075059777 @default.
• W2016365513 cites W2075739751 @default.
• W2016365513 cites W2076549445 @default.
• W2016365513 cites W2079076987 @default.
• W2016365513 cites W2084874525 @default.
• W2016365513 cites W2091712343 @default.
• W2016365513 cites W2106189359 @default.
• W2016365513 cites W2115869719 @default.
• W2016365513 cites W2121774805 @default.
• W2016365513 cites W2124021652 @default.
• W2016365513 cites W2124062214 @default.
• W2016365513 cites W2129381979 @default.
• W2016365513 cites W2143860178 @default.
• W2016365513 cites W2146274229 @default.
• W2016365513 cites W2151338055 @default.
• W2016365513 cites W2159882433 @default.
• W2016365513 cites W2165908283 @default.
• W2016365513 doi "https://doi.org/10.1038/nature10726" @default.
• W2016365513 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3257422" @default.
• W2016365513 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22190039" @default.
• W2016365513 hasPublicationYear "2011" @default.
• W2016365513 type Work @default.
• W2016365513 sameAs 2016365513 @default.
• W2016365513 citedByCount "316" @default.
• W2016365513 countsByYear W20163655132012 @default.
• W2016365513 countsByYear W20163655132013 @default.
• W2016365513 countsByYear W20163655132014 @default.
• W2016365513 countsByYear W20163655132015 @default.
• W2016365513 countsByYear W20163655132016 @default.
• W2016365513 countsByYear W20163655132017 @default.
• W2016365513 countsByYear W20163655132018 @default.
• W2016365513 countsByYear W20163655132019 @default.
• W2016365513 countsByYear W20163655132020 @default.
• W2016365513 countsByYear W20163655132021 @default.
• W2016365513 countsByYear W20163655132022 @default.
• W2016365513 countsByYear W20163655132023 @default.
• W2016365513 crossrefType "journal-article" @default.
• W2016365513 hasAuthorship W2016365513A5007856961 @default.
• W2016365513 hasAuthorship W2016365513A5008853854 @default.
• W2016365513 hasAuthorship W2016365513A5011859731 @default.
• W2016365513 hasAuthorship W2016365513A5014356370 @default.
• W2016365513 hasAuthorship W2016365513A5035411478 @default.
• W2016365513 hasAuthorship W2016365513A5038592699 @default.
• W2016365513 hasAuthorship W2016365513A5047407682 @default.
• W2016365513 hasAuthorship W2016365513A5047547845 @default.
• W2016365513 hasAuthorship W2016365513A5051099055 @default.
• W2016365513 hasAuthorship W2016365513A5051539758 @default.
• W2016365513 hasAuthorship W2016365513A5055678278 @default.
• W2016365513 hasAuthorship W2016365513A5063796166 @default.
• W2016365513 hasAuthorship W2016365513A5069150872 @default.
• W2016365513 hasAuthorship W2016365513A5072548895 @default.
• W2016365513 hasAuthorship W2016365513A5078210617 @default.
• W2016365513 hasBestOaLocation W20163655132 @default.
• W2016365513 hasConcept C104317684 @default.
• W2016365513 hasConcept C134459356 @default.
• W2016365513 hasConcept C153911025 @default.
• W2016365513 hasConcept C180754005 @default.
• W2016365513 hasConcept C25602115 @default.

• next