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

描述(由申请人提供)：该项目的长期目标是表征新的细胞-细胞和细胞-细胞外基质(ECM)相互作用，这些相互作用对中枢神经系统的正常发育至关重要，并由少突胶质细胞衍生的分子介导。识别这些新的机制不仅将促进我们对少突胶质细胞在发育过程中的功能作用的理解，还将有助于开发新的治疗策略，用于治疗多发性硬化症(MS)等病理性脱髓鞘疾病。这些研究的中心假设是，少突胶质细胞衍生蛋白磷酸二酯酶-Lα/自体趋化蛋白(PD-Iα/ATx)在细胞外基质和/或对少突胶质细胞功能至关重要的一条尚未确定的分子途径的细胞-细胞相互作用中发挥重要作用。这一假说将在以下特定目标中得到验证：1.确定PD-Iα/ATX的少突胶质细胞亚型调节少突胶质细胞-ECM相互作用和少突胶质细胞运动的能力；2.确定PD-Iα/AIX亚型的潜在中枢神经系统结合伙伴。本项目中提议的研究将为进一步研究PD-Iα/ATX在中枢神经系统中的作用提供继续研究的基础。在当前和未来的研究中获得的数据将提供可能有助于推进脱髓鞘疾病患者的新疗法的知识。

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.