مورد إلكتروني
Inhibition of Upf2-Dependent Nonsense-Mediated Decay Leads to Behavioral and Neurophysiological Abnormalities by Activating the Immune Response
| العنوان: | Inhibition of Upf2-Dependent Nonsense-Mediated Decay Leads to Behavioral and Neurophysiological Abnormalities by Activating the Immune Response |
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| المؤلفون: | Johnson, Jennifer L, Stoica, Loredana, Liu, Yuwei, Zhu, Ping Jun, Bhattacharya, Abhisek, Buffington, Shelly, Huq, Redwan, Eissa, N Tony, Larsson, Ola, Porse, Bo T, Domingo, Deepti, Nawaz, Urwah, Carroll, Renee, Jolly, Lachlan, Scerri, Tom S, Kim, Hyung-Goo, Brignell, Amanda, Coleman, Matthew J, Braden, Ruth, Kini, Usha, Jackson, Victoria, Baxter, Anne, Bahlo, Melanie, Scheffer, Ingrid E, Amor, David J, Hildebrand, Michael S, Bonnen, Penelope E, Beeton, Christine, Gecz, Jozef, Morgan, Angela T, Costa-Mattioli, Mauro |
| المصدر: | Johnson , J L , Stoica , L , Liu , Y , Zhu , P J , Bhattacharya , A , Buffington , S , Huq , R , Eissa , N T , Larsson , O , Porse , B T , Domingo , D , Nawaz , U , Carroll , R , Jolly , L , Scerri , T S , Kim , H-G , Brignell , A , Coleman , M J , Braden , R , Kini , U , Jackson , V , Baxter , A , Bahlo , M , Scheffer , I E , Amor , D J , Hildebrand , M S , Bonnen , P E , Beeton , C , Gecz , J , Morgan , A T & Costa-Mattioli , M 2019 , ' Inhibition of Upf2-Dependent Nonsense-Mediated Decay Leads to Behavioral and Neurophysiological Abnormalities by Activating the Immune Response ' , Neuron , vol. 104 , no. 4 , pp. 665-679 . |
| بيانات النشر: | 2019 |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | In 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. |
| مصطلحات الفهرس: | article |
| URL: | |
| الإتاحة: | Open access content. Open access content info:eu-repo/semantics/openAccess |
| ملاحظة: | English |
| أرقام أخرى: | DAV oai:pure.atira.dk:publications/5f7abb30-36a6-495a-be6e-42dcf50f7331 https://curis.ku.dk/portal/da/publications/inhibition-of-upf2dependent-nonsensemediated-decay-leads-to-behavioral-and-neurophysiological-abnormalities-by-activating-the-immune-response(5f7abb30-36a6-495a-be6e-42dcf50f7331).html https://doi.org/10.1016/j.neuron.2019.08.027 1322733009 |
| المصدر المساهم: | UNIV OF COPENHAGEN From OAIster®, provided by the OCLC Cooperative. |
| رقم الأكسشن: | edsoai.on1322733009 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |