Elucidating Neuron-Intrinsic Molecular Mechanisms of Optic Nerve Regeneration

阐明视神经再生的神经元固有分子机制

基本信息

批准号：
9438581
负责人：
Yang Hu
金额：
$ 25.38万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-12-01 至 2019-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9438581
关键词：
Elucidating Neuron Intrinsic Molecular Mechanisms

项目摘要

DESCRIPTION (provided by applicant): Injuries of mature central nervous system (CNS) axons result in loss of vital functions due to the failure of CNS axons regeneration. Neutralizing extracellular inhibitory molecules yields only limited regeneration or functional recovery in vivo, suggesting a critical role for neuron-intrinsic factors. As it has become apparent that the PTEN/mTOR pathway is critical for CNS axon regeneration, understanding the regrowth control of this pathway represents the first step toward developing novel therapeutic approaches to neural injury. Unfortunately, mTOR over-activity can result in tumor formation, metabolic diseases, and neurological disorders. It is therefore critically important to identify the specific downstream effectors by which PTEN/mTOR promotes axon regeneration, and to isolate them from other targets that mediate mTOR's deleterious effects. Using the anatomical and technical advantages of retinal ganglion cell and optic nerve as a CNS injury model, we have identified crucial regulators of axon growth, and are now ideally positioned to elucidate the downstream mechanisms by which PTEN/mTOR stimulates regeneration in mature CNS axons and identify translational targets of PTEN/mTOR govern adult CNS axon regeneration. These effectors are ideal therapeutic targets to promote regeneration in CNS injury and diseases, which can be selectively activated without activating other, potentially harmful pathways, thus to assist in safely translating our findings into novel neural repair treatments to preserve vital functions in patients with CNS injuries.

描述（由申请人提供）：由于中枢神经系统轴突再生失败，成熟中枢神经系统（CNS）轴突的损伤导致重要功能丧失，中和细胞外抑制分子仅产生有限的体内再生或功能恢复。表明神经元内在因素的关键作用已经变得明显，PTEN/mTOR 通路对于 CNS 轴突再生至关重要，了解该通路的再生控制代表了开发新的神经损伤治疗方法的第一步。 mTOR 过度活跃可导致肿瘤形成、代谢疾病和神经系统疾病，因此确定具体的原因至关重要。我们利用视网膜神经节细胞和视神经作为中枢神经系统损伤模型的解剖学和技术优势，确定了 PTEN/mTOR 促进轴突再生的下游效应器，并将它们与介导 mTOR 有害作用的其他靶点分离。生长，现在非常适合阐明 PTEN/mTOR 刺激成熟 CNS 轴突再生的下游机制，并确定 PTEN/mTOR 控制的翻译靶标这些效应器是促进中枢神经系统损伤和疾病再生的理想治疗靶点，可以选择性地激活而不激活其他潜在有害的途径，从而有助于将我们的研究结果安全地转化为新型神经修复疗法，以保留重要功能。中枢神经系统损伤患者。