New Mechanisms in Axon Regeneration

 描述(申请人提供)：轴突再生是神经系统的一种基本和保守的特性。但是，虽然轴突再生可以恢复神经损伤后的功能，但再生往往失败。因此，该领域的一个关键问题是发现是什么决定了受损神经元的再生能力。这项建议研究了在受损神经元中发挥作用并帮助确定是否发生再生的新机制。长期目标是全面了解将神经元损伤与成功再生联系起来的细胞功能。这个项目的具体目标是分析在遗传、细胞和分子水平上调节轴突再生的三种新的和相互关联的机制。该项目使用了体内方法的组合，最终分析了单个神经元的损伤反应。中心假设是，这三种新机制在调节轴突再生和神经元损伤反应的途径中发挥作用。然而，每个目标都是独立的，将导致关于轴突再生的细胞生物学的基础发现，即使各个机制是并行运行的，而不是以线性路径运行的。每个目标都得到了大量的初步数据以及新的生物学概念和实验方法的支持。完成这些目标将描述调节轴突再生的基本细胞机制。

 DESCRIPTION (provided by applicant): Axon regeneration is a fundamental and conserved property of nervous systems. But although axon regeneration can restore function after nerve injury, regeneration often fails. Thus, a key question in the field is to discover what determines the regenerative capacity of injured neurons. This proposal investigates new mechanisms that function in the injured neuron and that help determine whether or not regeneration occurs. The long-term goal is to gain a comprehensive understanding of the cellular functions that link neuronal injury to successful regeneration. The specific goal of this project is to analyze three novel and interrelated mechanisms that regulate axon regeneration at the genetic, cellular, and molecular level. The project uses a combination of in vivo approaches that culminate in analysis of the injury response in individual neurons. The central hypothesis is that the three novel mechanisms act in a pathway that regulates axon regeneration and the neuronal injury response. However, each Aim is independent and will result in fundamental discoveries about the cell biology of axon regeneration even if the individual mechanisms operate in parallel rather than in a linear pathway. Each Aim is supported by extensive preliminary data, as well as by novel biological concepts and experimental approaches. Completion of these Aims will describe fundamental cellular mechanisms that mediate axon regeneration.