Insect GDNF:TTC fusion protein improves delivery of GDNF to mouse CNS.
Insect GDNF:TTC fusion protein improves delivery of GDNF to mouse CNS.
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昆虫 GDNF:TTC 融合蛋白可改善 GDNF 向小鼠中枢神经系统的传递。
DOI：
10.1016/j.bbrc.2009.10.083
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发表时间：
2009
影响因子：
3.1
通讯作者：
Francis,JonathanW
中科院分区：
文献类型：
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作者：
Li,Jianhong;Chian,Ru-Ju;Ay,Ilknur;Kashi,BrendaB;Celia,SamuelA;Tamrazian,Eric;Pepinsky,RBlake;Fishman,PaulS;BrownJr,RobertH;Francis,JonathanW
为了提高外源性胶质细胞源性神经营养因子（GDNF）在体内中枢神经系统运动神经元的传递，我们评估了重组GDNF：破伤风毒素C片段融合蛋白在小鼠中枢神经系统中的生物利用度和药理活性。肌内注射后，GDNF：TTC而不是重组GDNF（rGDNF）在脊髓腹角细胞内产生强烈的GDNF免疫染色。鞘内输注GDNF：TTC导致GDNF在腰髓中的组织浓度比用rGDNF治疗的小鼠高至少150倍。鞘内注射rGDNF、GDNF：TTC或TTC对腰髓胆碱乙酰转移酶和GFRα-1水平无明显影响，而侧脑室注射rGDNF和GDNF：TTC可引起体重明显减轻。这些研究表明，昆虫细胞衍生的GDNF：TTC在体内哺乳动物CNS中保留其双功能活性，并在肌内或鞘内施用后改善GDNF向脊髓的递送。
With a view toward improving delivery of exogenous glial cell line-derived neurotrophic factor (GDNF) to CNS motor neurons in vivo, we evaluated the bioavailability and pharmacological activity of a recombinant GDNF:tetanus toxin C-fragment fusion protein in mouse CNS. Following intramuscular injection, GDNF:TTC but not recombinant GDNF (rGDNF) produced strong GDNF immunostaining within ventral horn cells of the spinal cord. Intrathecal infusion of GDNF:TTC resulted in tissue concentrations of GDNF in lumbar spinal cord that were at least 150-fold higher than those in mice treated with rGDNF. While levels of immunoreactive choline acetyltransferase and GFRα-1 in lumbar cord were not altered significantly by intrathecal infusion of rGNDF, GDNF:TTC, or TTC, only rGDNF and GDNF:TTC caused significant weight loss following intracerebroventricular infusion. These studies indicate that insect cell-derived GDNF:TTC retains its bi-functional activity in mammalian CNS in vivo and improves delivery of GDNF to spinal cord following intramuscular- or intrathecal administration.