Elucidating Neuron-Intrinsic Molecular Mechanisms of Optic Nerve Regeneration

项目总结 成熟中枢神经系统(CNS)轴突损伤导致中枢神经系统衰竭导致生命功能丧失 轴突再生。我们之前对这些基因进行了广泛的分子解剖 PTEN/PI3K/AKT/mTOR复合体(MTORCs)信号网络，阐明了它们之间的交叉调节 机制，并最终确定了构成视神经的线性和平行信号 再生。然而，PTEN或AKT下游主动调节轴突的特定效应器 再生仍然是未知的。这是一项识别再生标记和真实允许信号的建议 比较相同基因的再生和非再生视网膜节细胞对轴突再生的影响 调制。这些信息将提供一个明确的促进再生的信号模式，它将指导我们 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 中枢神经系统损伤和神经退行性疾病的治疗。此外，它也是非常 重要的是确定神经保护和再生疗法如何相互作用，特别是保护 从变性中再生轴突可以增强它们的生存能力和生长能力，使它们能够达到全长。 随着视觉功能的恢复而再生。

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.