NONVIRAL DELIVERY OF NEUROPROTECTIVE PROTEINS TO NEURONS

一般而言，用于治疗CNS的新治疗剂的开发 疾病往往严重阻碍了许多物质的能力， 从血液进入大脑然而，由于运动神经元具有 许多轴突末梢位于血脑屏障外，它可能是 可以利用这些入口来选择性地递送治疗药物， 当这些神经细胞受伤或患病时，这些物质会被释放。的 本项目的目的是研究两种重组杂交瘤的疗效， 蛋白质作为潜在治疗药物的靶向递送剂 蛋白质到CNS神经元（特别是运动神经元）。这些混合 分别产生SOD：Tet 45 l和SMN：Tet 45 l蛋白， 联合收割机将破伤风毒素片段C的神经元靶向特性与 1）人类超氧化物的假定神经保护作用 歧化酶（SOD-1），一种抗氧化酶，或2）运动神经元存活 (SMN)蛋白质，一种新的蛋白质，其功能的缺失或丧失可能是 与脊髓肌肉萎缩有关中概述的实验 该方案旨在测试潜在的神经保护能力， 这些杂交蛋白质的体外和体内研究。

In general, the development of new therapeutic agents for treating CNS diseases is often severely hindered by the inability of many substances to enter the brain from the bloodstream. However, since motor neurons have numerous axon terminals located outside the blood-brain barrier, it may be possible to exploit these portals to selectively deliver therapeutic substances to these nerve cells when they are injured or diseased. The purpose of this project is to study the efficacy of two recombinant hybrid proteins as agents for the targeted delivery of potentially therapeutic proteins to CNS neurons (particularly motor neurons). These hybrid proteins, SOD:Tet45l and SMN:Tet45l, were respectively engendered to combine the neuron targeting properties of tetanus toxin fragment C with the putative neuroprotective effects of either 1) human superoxide dismutase (SOD-1), an antioxidant enzyme, or 2) survival motor neuron (SMN) protein, a novel protein whose absence or loss of function may be involved in the spinal muscular atrophies. The experiments outlined in this proposal are designed to test the potential neuroprotective ability of these hybrid proteins in vitro and in vivo.