Recombinant GDNF: tetanus toxin fragment C fusion protein produced from insect cells.
Recombinant GDNF: tetanus toxin fragment C fusion protein produced from insect cells.
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重组 GDNF：由昆虫细胞产生的破伤风毒素片段 C 融合蛋白。
DOI：
10.1016/j.bbrc.2009.05.079
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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;Celia,SamuelA;Kashi,BrendaB;Tamrazian,Eric;Matthews,JonathanC;Remington,MaryP;Pepinsky,RBlake;Fishman,PaulS;BrownJr,RobertH;Francis,JonathanW
胶质细胞源性神经营养因子 (GDNF) 对实验动物中枢神经系统运动神经元具有有效的促存活作用。然而，其对人类的治疗效果可能因大脑和脊髓的生物利用度差而受到限制。为了改善体内 GDNF 向 CNS 运动神经元的递送，我们产生了一种重组融合蛋白，该蛋白由与破伤风毒素的无毒神经元结合片段连接的大鼠 GDNF 组成。由昆虫细胞产生的重组 GDNF:TTC 是与野生型 GDNF 类似的可溶性同二聚体，并且具有 GDNF 和 TTC 活性的双功能。与重组大鼠 GDNF 一样，融合蛋白增加了经处理的 NB41A3-hGFRα-1 神经母细胞瘤细胞中免疫反应性磷酸 Akt 的水平。与 TTC 一样，GDNF:TTC 在体外以高亲和力和选择性结合固定化神经节苷脂 GT1b。这些结果支持进一步测试重组 GDNF:TTC 作为非病毒载体，以改善体内 GDNF 向脑和脊髓的递送。
Glial cell line-derived neurotrophic factor (GDNF) has potent survival-promoting effects on CNS motor neurons in experimental animals. Its therapeutic efficacy in humans, however, may have been limited by poor bioavailability to the brain and spinal cord. With a view toward improving delivery of GDNF to CNS motor neurons in vivo, we generated a recombinant fusion protein comprised of rat GDNF linked to the non-toxic, neuron-binding fragment of tetanus toxin. Recombinant GDNF:TTC produced from insect cells was a soluble homodimer like wild-type GDNF and was bi-functional with respect to GDNF and TTC activity. Like recombinant rat GDNF, the fusion protein increased levels of immunoreactive phosphoAkt in treated NB41A3-hGFRα-1 neuroblastoma cells. Like TTC, GDNF:TTC bound to immobilized ganglioside GT1b in vitro with high affinity and selectivity. These results support further testing of recombinant GDNF:TTC as a non-viral vector to improve delivery of GDNF to brain and spinal cord in vivo.