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Funded Studies

Involvement of CD200/CD200 Receptor Interactions in Inflammatory-mediated Pathology in PD

Inflammation has been shown in many diseases to be a destructive process when occurring under inappropriate circumstances. Based on a wide range of studies, it appears that dopaminergic neurons in the human substantia nigra are particularly sensitive to inflammatory damage. Severe loss of these neurons leads to Parkinson's disease (PD), and prevention of this is key to preventing PD. Animal models of PD have shown that different anti-inflammatory agents can significantly protect substantia nigra neurons. Although damaging inflammatory processes have been well characterized, cellular mechanisms also exist to deactivate inflammation. Recent data have identified that CD200 and CD200 receptor interactions have significant protective anti-inflammatory effects. CD200 is expressed on a number of cells including neurons, and binds to CD200 receptor, which is mainly restricted to macrophages and related cells such as microglia, the principal inflammation causing cells. Binding of CD200 to CD200 receptor leads to a reduction in the inflammation caused by the CD200 receptor-expressing cells. Our preliminary data showed that human substantia nigra neurons appear to have reduced levels of CD200 compared to other neurons, which suggests that reduced amounts of this protein in these cells could make them more susceptible to inflammation. This project will examine which factors affect how much CD200 is expressed by dopaminergic neurons, with the aim of understanding how they may be reducing CD200 expression in vivo. Similarly, this project will examine which factors affect how human microglia express CD200 receptor, with the particular aim of identifying which inflammatory factors may change CD200 receptor expression. Manipulation of these interactions, particularly with pharmacological agents, may provide a directed approach to preventing or reducing inflammatory-mediated dopaminergic cell loss in PD.


  • Douglas Walker, PhD

    Sun City, AZ United States

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