Functional analysis of PD-l alpha/ATX in the CNS

描述（由申请人提供）：本项目的长期目标是表征对正常CNS发育至关重要且由少突胶质细胞衍生分子介导的新型细胞-细胞和细胞-细胞外基质（ECM）相互作用。识别这些新的机制不仅将促进我们对发育过程中少突胶质细胞功能作用的理解，而且还将有助于开发病理性脱髓鞘疾病（如多发性硬化症（MS））的新治疗策略。所提出的研究的中心假设是少突胶质细胞衍生的蛋白磷酸二酯酶-l α/自分泌运动因子（PD-I α/ATX）在细胞-ECM和/或细胞-细胞相互作用中起重要作用，所述细胞-ECM和/或细胞-细胞相互作用是对少突胶质细胞功能至关重要的尚未表征的分子途径。这一假设将在以下具体目标进行测试：1。确定少突胶质细胞来源的PD-I α/ATX亚型调节少突胶质细胞-ECM相互作用和少突胶质细胞运动性的能力; 2.鉴定少突胶质细胞衍生的PD-I α/AIX亚型的潜在CNS结合伴侣。本项目中提出的研究将为进一步研究PD-I α/ATX在CNS中的作用提供基础。在当前和未来的研究中获得的数据将提供可能有助于促进脱髓鞘疾病患者新治疗的知识。

DESCRIPTION (provided by applicant): The long-term goal of this project is to characterize novel cell-cell and cell-extracellular matrix (ECM) interactions that are crucial for normal CNS development and that are mediated by oligodendrocyte-derived molecules. Identifying these novel mechanisms will not only advance our understanding about the functional role of oligodendrocytes during development but will also contribute to the development of novel therapeutic strategies in pathological, demyelinating diseases, such as Multiple Sclerosis (MS). The central hypothesis of the proposed studies is that the oligodendrocyte-derived protein phosphodiesterase-l alpha/autotaxin (PD-I alpha/ATX) plays an essential role in celI-ECM and/or cell-cell interactions of a yet uncharacterized molecular pathway that is critical for oligodendrocyte function. This hypothesis will be tested in the following specific aims: 1. To determine the capacity of the oligodendrocyte-denved isoforms of PD-I alpha/ATX to modulate oligodendrocyte-ECM interactions and oligodendrocyte motility; 2. To identify potential CNS binding partners of the oligodendrocyte-derived isoforms of PD-I alpha/AIX. The studies proposed in this project will provide the basis for continuing research that will further examine the role of PD-I alpha/ATX in the CNS. The data obtained in current and future studies will provide knowledge that is likely to contribute to the advancement of novel treatments of patients with demyelinating diseases.