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Synapse ; 61(12): 971-7, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17879263

RESUMO

To study the potential benefit of the NURR1 gene in Parkinson's disease (PD), we constructed a recombinant republic-deficit adenovirus containing the NURR1 gene (Ad-NURR1) and expressed it in transplanted neural stem cells (NSC). Ad-NURR1 was constructed, and NURR1 mRNA and protein expression were identified by in situ hybridization and western blot analysis, respectively. The identified NURR1 protein could directly or indirectly induce NSC differentiation into neurons. To identify a potential therapeutic use for the transfected NSCs, cells were transplanted into 6-hydroxydopamine lesioned rats. Histopathological and behavioral alterations were evaluated via immunohistochemistry and the ration test, respectively, in rats transplanted with NSCs with or without the Ad-NURR1 adenovirus. The Ad-NURR1 construct effectively expressed the NURR1 protein, which could directly or indirectly induce NSC differentiation into neurons. Both histopathological and behavioral alterations were seen in rats treated with NSCs with or without the Ad-NURR1 construct, although in the case of the latter, the benefits were more robust. These results suggest a potential therapeutic benefit for Ad-NURR1-expressing cells in the treatment of PD. The Ad-NURR1 modification induced NSC differentiation and therefore represents a potential therapy for PD.


Assuntos
Proteínas de Ligação a DNA/fisiologia , Terapia Genética/métodos , Neurônios/fisiologia , Doença de Parkinson/terapia , Células-Tronco/metabolismo , Fatores de Transcrição/fisiologia , Adenoviridae/fisiologia , Adrenérgicos/toxicidade , Animais , Comportamento Animal , Diferenciação Celular/genética , Linhagem Celular Transformada , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/ultraestrutura , Modelos Animais de Doenças , Humanos , Microscopia Eletrônica de Varredura/métodos , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares , Oxidopamina/toxicidade , Doença de Parkinson/etiologia , Doença de Parkinson/patologia , Ratos , Ratos Sprague-Dawley , Transplante de Células-Tronco/métodos , Fatores de Tempo , Fatores de Transcrição/genética , Fatores de Transcrição/ultraestrutura , Transfecção , Tirosina 3-Mono-Oxigenase/metabolismo
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