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MicroRNA-27a reduces mutant hutingtin aggregation in an in vitro model of Huntington's disease.
Ban, Jae-Jun; Chung, Jin-Young; Lee, Mijung; Im, Wooseok; Kim, Manho.
Afiliación
  • Ban JJ; Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
  • Chung JY; Department of Veterinary Internal Medicine and Geriatrics, College of Veterinary Medicine, Kangwon National University, Gangwon, South Korea.
  • Lee M; Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
  • Im W; Department of Neurology, Seoul National University Hospital, Seoul, South Korea; Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, South Korea. Electronic address: imwooseok@gmail.com.
  • Kim M; Department of Neurology, Seoul National University Hospital, Seoul, South Korea; Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, South Korea; Protein Metabolism Medical Research Center, College of Medicine, Seoul National University, Seoul, South Korea. Electro
Biochem Biophys Res Commun ; 488(2): 316-321, 2017 06 24.
Article en En | MEDLINE | ID: mdl-28495533
Huntington's disease (HD) is a fatal genetic disease caused by abnormal aggregation of mutant huntingtin protein (mHtt). Reduction of mHtt aggregation decreases cell death of the brain and is a promising therapeutic strategy of HD. MicroRNAs are short non-coding nucleotides which modulate various genes and dysregulated in many diseases including HD. MicroRNA miR-27a was reported to be reduced in the brain of R6/2 HD mouse model and modulate multidrug resistance protein-1 (MDR-1). Using subventricular zone-derived neuronal stem cells (NSCs), we used in vitro HD model to test the effect of miR-27a on MDR-1 and mHtt aggregation. R6/2-derived NSCs can be differentiated under condition of growth factor deprivation, and the progression of differentiation leads to a decrease of MDR-1 level and efflux function of cells. Immunocytochemistry result also confirmed that mHtt aggregation was increased with differentiation. We transfected miR-27a in the R6/2-derived differentiated NSCs, and examined phenotype of HD, mHtt aggregation. As a result, miR-27a transfection resulted in reduction of mHtt aggregation in HD cells. In addition, MDR-1, which can transport mHtt, protein level was increased by miR-27a transfection. Conversely, knock-down of MDR-1 through MDR-1 siRNA increased mHtt aggregation in vitro. Our results indicate that miR-27a could reduce mHtt level of the HD cell by augmenting MDR-1 function.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Huntington / MicroARNs / Modelos Animales de Enfermedad / Agregado de Proteínas / Proteína Huntingtina Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Biochem Biophys Res Commun Año: 2017 Tipo del documento: Article País de afiliación: Corea del Sur Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Huntington / MicroARNs / Modelos Animales de Enfermedad / Agregado de Proteínas / Proteína Huntingtina Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Biochem Biophys Res Commun Año: 2017 Tipo del documento: Article País de afiliación: Corea del Sur Pais de publicación: Estados Unidos