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

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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.