دورية أكاديمية
Rhes suppression enhances disease phenotypes in Huntington's disease mice.
| العنوان: | Rhes suppression enhances disease phenotypes in Huntington's disease mice. |
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| المؤلفون: | Lee JH; Medical Scientist Training Program, Roy J and Lucille A Carver College of Medicine, Iowa City, IA, USA Department of Molecular Physiology & Biophysics, Roy J and Lucille A Carver College of Medicine, Iowa City, IA, USA., Sowada MJ; Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine, Iowa City, IA, USA., Boudreau RL; Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine, Iowa City, IA, USA., Aerts AM; Department of Psychiatry, Roy J and Lucille A Carver College of Medicine, Iowa City, IA, USA., Thedens DR; Department of Radiology, Roy J and Lucille A Carver College of Medicine, Iowa City, IA, USA., Nopoulos P; Department of Psychiatry, Roy J and Lucille A Carver College of Medicine, Iowa City, IA, USA., Davidson BL; Department of Molecular Physiology & Biophysics, Roy J and Lucille A Carver College of Medicine, Iowa City, IA, USA Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine, Iowa City, IA, USA Department of Neurology, Roy J and Lucille A Carver College of Medicine, Iowa City, IA, USA. |
| المصدر: | Journal of Huntington's disease [J Huntingtons Dis] 2014; Vol. 3 (1), pp. 65-71. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: IOS Press Country of Publication: Netherlands NLM ID: 101589965 Publication Model: Print Cited Medium: Print ISSN: 1879-6397 (Print) Linking ISSN: 18796397 NLM ISO Abbreviation: J Huntingtons Dis Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam, The Netherlands : IOS Press |
| مواضيع طبية MeSH: | MicroRNAs*, GTP-Binding Proteins/*antagonists & inhibitors , Huntington Disease/*metabolism , Mutant Proteins/*metabolism , Neostriatum/*pathology , Nerve Tissue Proteins/*metabolism , Nuclear Proteins/*metabolism, Animals ; Anxiety/metabolism ; Atrophy ; Behavior, Animal ; Disease Models, Animal ; Genetic Therapy ; Huntingtin Protein ; Huntington Disease/genetics ; Magnetic Resonance Imaging ; Phenotype |
| مستخلص: | In Huntington's disease (HD) mutant HTT is ubiquitously expressed yet the striatum undergoes profound early degeneration. Cell culture studies suggest that a striatal-enriched protein, Rhes, may account for this vulnerability. We investigated the therapeutic potential of silencing Rhes in vivo using inhibitory RNAs (miRhes). While Rhes suppression was tolerated in wildtype mice, it failed to improve rotarod function in two distinct HD mouse models. Additionally, miRhes treated HD mice had increased anxiety-like behaviors and enhanced striatal atrophy as measured by longitudinal MRI when compared to control treated mice. These findings raise caution regarding the long-term implementation of inhibiting Rhes as a therapy for HD. |
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| معلومات مُعتمدة: | T32 HL007121 United States HL NHLBI NIH HHS; P01 NS050210 United States NS NINDS NIH HHS; NS50210 United States NS NINDS NIH HHS; R01 NS055903 United States NS NINDS NIH HHS; NS076631 United States NS NINDS NIH HHS; NS050568-03 United States NS NINDS NIH HHS; R01 NS076631 United States NS NINDS NIH HHS; R01 NS050568 United States NS NINDS NIH HHS; T32 GM007337 United States GM NIGMS NIH HHS |
| فهرسة مساهمة: | Keywords: Huntington disease; RNA interference; Rhes; genetic therapies; neurodegenerative disease; rasd2 |
| المشرفين على المادة: | 0 (Htt protein, mouse) 0 (Huntingtin Protein) 0 (MicroRNAs) 0 (Mutant Proteins) 0 (Nerve Tissue Proteins) 0 (Nuclear Proteins) EC 3.6.1.- (GTP-Binding Proteins) EC 3.6.1.- (Rasd2 protein, mouse) |
| تواريخ الأحداث: | Date Created: 20140727 Date Completed: 20141027 Latest Revision: 20211021 |
| رمز التحديث: | 20240829 |
| مُعرف محوري في PubMed: | PMC4139702 |
| DOI: | 10.3233/JHD-140094 |
| PMID: | 25062765 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1879-6397 |
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| DOI: | 10.3233/JHD-140094 |