Factors Affecting Regeneration Through the Glial Scar

描述（由申请人提供）：根据克里斯托弗和达纳里夫基金会有超过100万人脊髓损伤（SCI）在美国。制定策略以促进SCI后的再生和功能恢复一直是一个长期且具有挑战性的目标。虽然我们的实验室是第一个认识到硫酸化蛋白聚糖在再生失败中的关键作用，但产生这种抑制性细胞外基质分子家族的细胞阻断再生的机制在很大程度上是未知的。再生，虽然营养不良，轴突持续和紧密地与一群前体细胞在病变的核心，产生什么被认为是一个强大的抑制蛋白聚糖称为NG2。这些NG2细胞的作用和据称是再生失败中的主要蛋白聚糖已经变得非常有争议。我们提出的研究将首次揭示这些细胞表面上的这种高度优先生长如何导致粘合剂截留现象，这可能是再生失败的关键决定因素。我们提出的研究还将建立在神经元上的一个受体家族的令人兴奋的发现的基础上，我们提出通过过强的粘附机制来介导CSPGs的抑制作用。深入了解导致轴突长期滞留在胶质瘢痕内的复杂的细胞和分子相互作用，将使我们能够设计出用于阻断或克服这些不良相互作用的改进技术，并有助于寻找刺激胶质瘢痕之外的强大再生的策略。

DESCRIPTION (provided by applicant): According to the Christopher and Dana Reeve Foundation there are more than 1 million people with spinal cord injury (SCI) in the US. Developing strategies to promote regeneration and functional recovery after SCI has been a long and challenging goal. Although our lab was the first to recognize the critical role of sulfated proteoglycans in regeneration failure, the mechanisms by which the cells that produce this family of inhibitory extracellular matrix molecules block regeneration is largely unknown. Regenerating, albeit dystrophic, axons continually and tightly associate with a cohort of precursor cells in the core of the lesion that produce what is thought to be a potently inhibitory proteoglycan called NG2. The role of these NG2 cells and what has been purported to be a major proteoglycan in regeneration failure has become highly controversial. Our proposed studies will reveal for the first time how such highly preferred growth upon the surface of these cells results in an adhesive entrapment phenomenon that is likely to be a critical determinant in regeneration failure. Our proposed studies will also build upon the exciting discovery of a family of receptors on neurons that mediate, we propose via overly strong adhesive mechanisms, the inhibitory actions of CSPGs. Understanding in depth the complicated cellular and molecular interactions that lead to long term entrapment of axons within the glial scar will allow us to devise improved techniques for blocking or overcoming these untoward interactions and help in the search for strategies to stimulate robust regeneration beyond the glial scar.)