Mechanisms of Corticospinal Tract Regeneration

这个项目致力于发现诱导皮质脊髓束再生的方法。 (CST与脊髓损伤后运动功能的恢复。CST是一条 对自愿行动的能力负责。脊髓损伤对CST的损害 受伤是人们瘫痪的原因。该项目基于CST可以 通过靶向分子通路诱导脊髓损伤后再生 控制发育中的细胞生长，特别是磷酸酶和张力蛋白同源物(PTEN)。PTEN 负责关闭对细胞生长至关重要的蛋白质合成类型 发展。PTEN通过阻断雷帕霉素的哺乳动物靶点(MTOR)发挥作用，因此缺失 PTEN对mTOR的抑制作用，进而允许细胞合成 对细胞生长至关重要。我们已经证明，PTEN在小鼠和小鼠中的基因缺失 AAVshRNA基因敲除大鼠PTEN基因使CST神经元 再生反应，伴随着运动功能的恢复。新项目是 基于令人兴奋的最新发现，靶向PTEN在成人神经细胞中诱导 一种青春活力的状态，在这种状态下，除了有再生的能力外，还会有永久的成长 受伤后。该项目的总体目标是确定细胞和分子 这种生长使能状态的机制，并识别开启或关闭的基因 在生长和再生过程中。定义基因表达的模式，这是 神经细胞的生长激活状态将确定未来治疗干预的靶点 促进损伤后的再生和修复，潜在地保护神经细胞免受 神经退行性疾病中的变性。

This project is dedicated to discovering ways to induce regeneration of the corticospinal tract (CST and recovery of motor function after spinal cord injury (SCI). The CST is the pathway that is responsible for the ability to move voluntarily. Damage to the CST as a result of a spinal cord injury is the reason people are paralyzed. The project is based on discoveries that the CST can be induced to regenerate following spinal cord injury by targeting molecular pathways that control cell growth in development, specifically phosphatase and tensin homolog (PTEN). PTEN is responsible for shutting down the type of protein synthesis that is critical for cell growth during development. PTEN acts by blocking the mammalian target of Rapamycin, (mTOR), so deletion of PTEN releases inhibition on mTOR, which in turn allows the cell to synthesize proteins that are critical for cell growth. We have shown that genetic deletion of PTEN in mice and knockdown of PTEN in rats with AAVshRNA allows CST neurons to mount a robust regenerative response, which is accompanied by recovery of motor function. The new project is based on exciting and novel recent discoveries that targeting PTEN in adult nerve cells induces a state of youthful vigor in which there is perpetual growth in addition to an ability to regenerate after injury. The overall goal of the project is to determine the cellular and molecular mechanisms of this growth-enabled state and identify the genes that are turned on or shut off during growth and regeneration. Defining the pattern of gene expression that underlies the growth-enabled state in nerve cells will identify targets for future therapeutic interventions to promote regeneration and repair after injury and potentially protect nerve cells from degeneration in neurodegenerative disorders.