Netrins and Gene Therapy After Spinal Cord Injury

描述(由申请人提供)： 在过去的二十年里，临床前研究的进步起到了一定的作用 据我们所知，脊髓损伤后可以促进轴突生长的因素。然而，信息相对匮乏。 关于可能增强和引导轴突生长的分子机制 成人受伤。一个重要的分子家族，发挥着重要的 在轴突生长和发育过程中的指导作用是Netrin家族 可扩散分子及其相关受体，DCC(删除的冒号 癌)和UNC-5家族蛋白。这个项目的特点是 网织蛋白及其受体在成人脊髓损伤后的自然表达， 然后操纵轴突对这些分子做出反应的潜在能力 用网织蛋白基因体外传递到损伤的脊髓。两个具体的 我们将考察AIMS： 具体目标1：表征netrins及其受体的表达(成员 DCC和UNC-5家族的成员)。 特定目标2：确定网织蛋白在受伤成人中是否过度表达 脊髓影响轴突生长的范围或方向。

DESCRIPTION (provided by applicant): Progress in preclinical research over the last two decades has contributed substantially to our knowledge of factors that can promote axonal growth after spinal cord injury. However, there is a relative paucity of information regarding molecular mechanisms that might augment and guide axonal growth after injury in the adult. One important family of molecules that plays an important role in axon growth and guidance during development is the netrin family of diffusible molecules, and their associated receptors, DCC (deleted colon carcinoma) and UNC-5 family proteins. This project will characterize the natural expression of netrin and its receptors after adult spinal cord injury, then manipulate the potential ability of axons to respond to these molecules using ex vivo gene delivery of netrin to the injured spinal cord. Two specific aims will be examined: Specific Aim 1: Characterize expression of netrins and their receptors (members of the DCC and UNC-5 family) in the intact and lesioned adult rat spinal cord. Specific Aim 2: Determine whether netrin over-expression in the injured adult spinal cord influences the extent or direction of axonal growth.