胶质细胞源性神经生长因子
MPTP公司
黑质
神经营养因子
多巴胺能
纹状体
神经科学
帕金森病
灵长类动物
黑质纹状体通路
神经退行性变
生物
多巴胺
医学
内科学
疾病
受体
作者
Jeffrey H. Kordower,Marina E. Emborg,Jocelyne Bloch,Shuang Yang,Yaping Chu,Liza Leventhal,Jodi L. McBride,Er‐Yun Chen,Stéphane Palfi,Ben Roitberg,William D. Brown,James E. Holden,Robert W. Pyzalski,Michael D. Taylor,Paul M. Carvey,Zaodung Ling,Didier Trono,Philippe Hantraye,Nicole Déglon,Patrick Aebischer
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2000-10-27
卷期号:290 (5492): 767-773
被引量:1208
标识
DOI:10.1126/science.290.5492.767
摘要
Lentiviral delivery of glial cell line-derived neurotrophic factor (lenti-GDNF) was tested for its trophic effects upon degenerating nigrostriatal neurons in nonhuman primate models of Parkinson's disease (PD). We injected lenti-GDNF into the striatum and substantia nigra of nonlesioned aged rhesus monkeys or young adult rhesus monkeys treated 1 week prior with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Extensive GDNF expression with anterograde and retrograde transport was seen in all animals. In aged monkeys, lenti-GDNF augmented dopaminergic function. In MPTP-treated monkeys, lenti-GDNF reversed functional deficits and completely prevented nigrostriatal degeneration. Additionally, lenti-GDNF injections to intact rhesus monkeys revealed long-term gene expression (8 months). In MPTP-treated monkeys, lenti-GDNF treatment reversed motor deficits in a hand-reach task. These data indicate that GDNF delivery using a lentiviral vector system can prevent nigrostriatal degeneration and induce regeneration in primate models of PD and might be a viable therapeutic strategy for PD patients.
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