Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/21853
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dc.contributor.authorJohnson, Jennifer L-
dc.contributor.authorStoica, Loredana-
dc.contributor.authorLiu, Yuwei-
dc.contributor.authorZhu, Ping Jun-
dc.contributor.authorBhattacharya, Abhisek-
dc.contributor.authorBuffington, Shelly-
dc.contributor.authorHuq, Redwan-
dc.contributor.authorEissa, N Tony-
dc.contributor.authorLarsson, Ola-
dc.contributor.authorPorse, Bo T-
dc.contributor.authorDomingo, Deepti-
dc.contributor.authorNawaz, Urwah-
dc.contributor.authorCarroll, Renee-
dc.contributor.authorJolly, Lachlan-
dc.contributor.authorScerri, Tom S-
dc.contributor.authorKim, Hyung-Goo-
dc.contributor.authorBrignell, Amanda-
dc.contributor.authorColeman, Matthew J-
dc.contributor.authorBraden, Ruth-
dc.contributor.authorKini, Usha-
dc.contributor.authorJackson, Victoria-
dc.contributor.authorBaxter, Anne-
dc.contributor.authorBahlo, Melanie-
dc.contributor.authorScheffer, Ingrid E-
dc.contributor.authorAmor, David J-
dc.contributor.authorHildebrand, Michael S-
dc.contributor.authorBonnen, Penelope E-
dc.contributor.authorBeeton, Christine-
dc.contributor.authorGecz, Jozef-
dc.contributor.authorMorgan, Angela T-
dc.contributor.authorCosta-Mattioli, Mauro-
dc.date2019-09-27-
dc.date.accessioned2019-10-07T04:41:33Z-
dc.date.available2019-10-07T04:41:33Z-
dc.date.issued2019-10-01-
dc.identifier.citationNeuron 2019; 104(4): 665-679.e8-
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/21853-
dc.description.abstractIn humans, disruption of nonsense-mediated decay (NMD) has been associated with neurodevelopmental disorders (NDDs) such as autism spectrum disorder and intellectual disability. However, the mechanism by which deficient NMD leads to neurodevelopmental dysfunction remains unknown, preventing development of targeted therapies. Here we identified novel protein-coding UPF2 (UP-Frameshift 2) variants in humans with NDD, including speech and language deficits. In parallel, we found that mice lacking Upf2 in the forebrain (Upf2 fb-KO mice) show impaired NMD, memory deficits, abnormal long-term potentiation (LTP), and social and communication deficits. Surprisingly, Upf2 fb-KO mice exhibit elevated expression of immune genes and brain inflammation. More importantly, treatment with two FDA-approved anti-inflammatory drugs reduced brain inflammation, restored LTP and long-term memory, and reversed social and communication deficits. Collectively, our findings indicate that impaired UPF2-dependent NMD leads to neurodevelopmental dysfunction and suggest that anti-inflammatory agents may prove effective for treatment of disorders with impaired NMD.-
dc.language.isoeng-
dc.subjectautism-
dc.subjectimmune response-
dc.subjectmRNA quality control-
dc.subjectmemory-
dc.subjectneurodevelopmental disorders-
dc.subjectspeech disorder-
dc.titleInhibition of Upf2-Dependent Nonsense-Mediated Decay Leads to Behavioral and Neurophysiological Abnormalities by Activating the Immune Response.-
dc.typeJournal Article-
dc.identifier.journaltitleNeuron-
dc.identifier.affiliationDepartment of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA; Memory and Brain Research Center, Baylor College of Medicine, Houston, TX 77030, USAen
dc.identifier.affiliationAdelaide Medical School and Robinson Research Institute, The University of Adelaide, Adelaide 5005, Australiaen
dc.identifier.affiliationSchool of Biological Sciences, The University of Adelaide, Adelaide 5005, Australiaen
dc.identifier.affiliationDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USAen
dc.identifier.affiliationMurdoch Children's Research Institute, Parkville, VIC 3052, Australiaen
dc.identifier.affiliationDepartment of Audiology and Speech Pathology, University of Melbourne, Melbourne, VIC 3010, Australiaen
dc.identifier.affiliationHealthy Mothers and Babies, South Australian Health and Medical Research Institute, Adelaide 5000, Australiaen
dc.identifier.affiliationThe Florey Institute of Neuroscience and Mental Health, Parkville, VIC 3010, Australiaen
dc.identifier.affiliationThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australiaen
dc.identifier.affiliationDepartment of Mathematics and Statistics, University of Melbourne, Melbourne, VIC 3010, Australiaen
dc.identifier.affiliationPopulation Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, University of Melbourne, Melbourne, VIC 3010, Australiaen
dc.identifier.affiliationDepartment of Medical Biology and School of Mathematics and Statistics, University of Melbourne, Melbourne, VIC 3010, Australiaen
dc.identifier.affiliationDepartment of Medicine, Baylor College of Medicine, Houston, TX 77030, USAen
dc.identifier.affiliationDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USAen
dc.identifier.affiliationBiotech Research and Innovation Center (BRIC), University of Copenhagen, Copenhagen 1165, Denmarken
dc.identifier.affiliationThe Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Copenhagen 1165, Denmarken
dc.identifier.affiliationDanish Stem Cell Centre (DanStem), Faculty of Health Sciences, University of Copenhagen, Copenhagen 1165, Denmarken
dc.identifier.affiliationDepartment of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USAen
dc.identifier.affiliationMemory and Brain Research Center, Baylor College of Medicine, Houston, TX 77030, USAen
dc.identifier.affiliationMurdoch Children's Research Institute, Parkville, VIC 3052, Australiaen
dc.identifier.affiliationDepartment of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationDepartment of Pediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, VIC 3052, Australiaen
dc.identifier.affiliationHunter Genetics, Hunter New England Local Health District, Newcastle 2298, NSW, Australiaen
dc.identifier.affiliationThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australiaen
dc.identifier.affiliationAdelaide Medical School and Robinson Research Institute, The University of Adelaide, Adelaide 5005, Australiaen
dc.identifier.affiliationDepartment of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA-
dc.identifier.affiliationDepartment of Oncology-Pathology, SciLifeLab, Karolinska Institutet, Solna 17165, Sweden-
dc.identifier.affiliationNeurological Disorders Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Doha 34110, Qatar-
dc.identifier.affiliationOxford Centre for Genomic Medicine, Oxford OX3 7JX, UK-
dc.identifier.affiliationDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA-
dc.identifier.affiliationDepartment of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA-
dc.identifier.doi10.1016/j.neuron.2019.08.027-
dc.identifier.orcid0000-0002-2311-2174-
dc.identifier.pubmedid31585809-
dc.type.austinJournal Article-
local.name.researcherHildebrand, Michael S
item.languageiso639-1en-
item.cerifentitytypePublications-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.grantfulltextnone-
item.openairetypeJournal Article-
item.fulltextNo Fulltext-
crisitem.author.deptEpilepsy Research Centre-
crisitem.author.deptEpilepsy Research Centre-
crisitem.author.deptMedicine (University of Melbourne)-
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