PLoS ONE：
神经损伤严重影响人类健康。中国科学院遗传发育所戴建武实验室与大连医科大学脑疾病研究所合作，在周围神经损伤后的再生研究中取得了重要进展。
神经细胞外基质中富含层粘连蛋白，在神经受到损伤时，受损部位的层粘连蛋白表达量升高。戴建武实验室研制了能特异与层粘连蛋白结合的基因工程重组人神经生长因子（LBD-NGF），提出了将神经受损部位的内源的层粘连蛋白同时作为LBD-NGF的结合靶点和神经再生的支架的科研思路。这一思路不久前在用与胶原特异结合的VEGF治疗心肌损伤中显示出优越性（Zhang et al, Circulation 2009）。
他们与合作者在大鼠坐骨神经钝挫伤模型中证明，神经受损部位的层粘连蛋白能够作为LBD-NGF的有效靶点。通过多种坐骨神经功能测试和组织学分析表明，LBD-NGF可以有效地促进坐骨神经的再生和功能恢复。戴建武研究员表示该实验是神经损伤修复研究长期目标的一个初步尝试。在外周神经大段缺失损伤修复时可能还需要支架材料。此外，LBD-NGF和生物材料及干细胞的联合使用是否更有利于神经损伤的修复，还需要进一步探索。这项成果为临床上神经损伤的治疗提供了新的思路。
这项工作以该实验室博士研究生孙文杰为第一作者发表在PLoS ONE上。该研究受中国科学院创新方向项目资助。（生物谷Bioon.com）
PLoS ONE 4(7): e6180. doi:10.1371/journal.pone.0006180
Improvement of Sciatic Nerve Regeneration Using Laminin-Binding Human NGF-β
Wenjie Sun1,2, Changkai Sun3, Hui Zhao3, Hang Lin1, Qianqian Han1, Jingyu Wang4, Hui Ma5, Bing Chen1, Zhifeng Xiao1, Jianwu Dai1*
1 Key laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China, 2 Graduate School, Chinese Academy of Sciences, Beijing, China, 3 Institute of Brain Disorders and the Key Lab for Brain Disorders of Liaoning Province, Dalian Medical University, Dalian, China, 4 Experimental Animal Center of Dalian Medical University, Dalian, China, 5 Department of Pharmaceutics, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
Background
Sciatic nerve injuries often cause partial or total loss of motor, sensory and autonomic functions due to the axon discontinuity, degeneration, and eventual death which finally result in substantial functional loss and decreased quality of life. Nerve growth factor (NGF) plays a critical role in peripheral nerve regeneration. However, the lack of efficient NGF delivery approach limits its clinical applications. We reported here by fusing with the N-terminal domain of agrin (NtA), NGF-β could target to nerve cells and improve nerve regeneration.
Methods
Laminin-binding assay and sustained release assay of NGF-β fused with NtA (LBD-NGF) from laminin in vitro were carried out. The bioactivity of LBD-NGF on laminin in vitro was also measured. Using the rat sciatic nerve crush injury model, the nerve repair and functional restoration by utilizing LBD-NGF were tested.
Findings
LBD-NGF could specifically bind to laminin and maintain NGF activity both in vitro and in vivo. In the rat sciatic nerve crush injury model, we found that LBD-NGF could be retained and concentrated at the nerve injury sites to promote nerve repair and enhance functional restoration following nerve damages.
Conclusion
Fused with NtA, NGF-β could bind to laminin specifically. Since laminin is the major component of nerve extracellular matrix, laminin binding NGF could target to nerve cells and improve the repair of peripheral nerve injuries
