Treatment of Parkinson disease with C17.2 neural stem cells overexpressing NURR1 with a recombined republic-deficit adenovirus containing the NURR1 gene.
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.
Li
Qing-Jun
QJ
Department of Neurology, Dong Guan People Hospital, Dong Guan 523018, China.
Tang
Ya-Mei
YM
Liu
Jun
J
Zhou
Dao-You
DY
Li
Xiang-Pen
XP
Xiao
Song-Hua
SH
Jian
Dong-Xing
DX
Xing
Yi-Gang
YG
D000256:Adenoviridae / Q000502:physiology; D018663:Adrenergic Agents / Q000633:toxicity; D000818:Animals; D001522:Behavior, Animal; D002454:Cell Differentiation / Q000235:genetics; D002461:Cell Line, Transformed; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008855:Microscopy, Electron, Scanning / Q000379:methods; D009474:Neurons / Q000502:physiology*; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D014162:Transfection; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018663:Adrenergic Agents; D004268:DNA-Binding Proteins; C539882:NR4A2 protein, human; C539884:Nr4a2 protein, rat; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D014157:Transcription Factors; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase