Elucidating Neuron-Intrinsic Molecular Mechanisms of Optic Nerve Regeneration

项目摘要 成熟的中枢神经系统（CNS）轴突损伤导致CNS功能衰竭而丧失生命功能 轴突再生我们之前对这些细胞进行了广泛的分子解剖， PTEN/PI 3 K/AKT/mTOR复合物（mTORCs）信号网络，阐明了它们的交叉调节作用。 机制，并明确确定了线性和平行的信号，有助于视神经 再生然而，主动调节轴突的PTEN或AKT下游的特异性效应物， 再生是未知的。这是一个建议，以确定再生标记和真正的许可信号 通过比较再生和非再生的RGC与相同的遗传 调变这些信息将提供一个明确的促再生信号模式， 确定新的治疗靶点，并协助安全地将我们的发现转化为创新的神经修复 治疗中枢神经系统损伤和神经退行性疾病的患者。此外，它也是极其 重要的是要确定神经保护和再生疗法如何相互作用，特别是是否保护 从退化中再生轴突增强了它们的活力和生长， 再生，恢复视觉功能。

PROJECT SUMMARY Injuries of mature central nervous system (CNS) axons result in loss of vital functions due to the failure of CNS axons regeneration. We previously conducted an extensive molecular dissection of the PTEN/PI3K/AKT/mTOR complexes (mTORCs) signaling network, illuminated their cross-regulating mechanisms, and definitively determined the linear and parallel signals that contribute to optic nerve regeneration. However, the specific effectors downstream of PTEN or AKT that proactively regulate axon regeneration are still unknown. This is a proposal to identify regeneration markers and true permissive signals of axon regeneration by comparing regenerating and non-regenerating RGCs with the same genetic modulation. This information will provide an unambiguous pro-regeneration signaling pattern that will guide us to identify novel therapeutic targets and assist in safely translating our findings into innovative neural repair treatments for patients with CNS injuries and neurodegenerative diseases. In addition, it is also extremely important to determine how neuroprotection and regeneration therapies interact, especially whether protecting regenerating axons from degeneration enhances their viability and growth so that they can achieve full-length regeneration with recovery of visual function.