Studies demonstrating that Nurr1 mRNA is upregulated by LPS in macrophages (Barish et al., 2005; Pei et al., 2005) raised the question of whether it might also be expressed in non-neuronal cells and influence the development of PD. Analysis of Nurr1 protein and mRNA levels in primary human and mouse microglia, primary human astrocytes, and the BV2 microglia cell line demonstrated significant protein expression under basal conditions and induction of Nurr1 mRNA in microglia in response to LPS (Fig. S1A–E and data not shown). Similarly, Nurr1 protein colocalized with the microglia marker F4/80 (Fig. S2E) and Nurr1 mRNA was induced approximately 2-fold in the SN 6h following stereotaxic injection of LPS (Fig. S1F). To investigate the potential role of Nurr1 in PD pathology, we evaluated the impact of reducing Nurr1 expression. Since Nurr1-deficient mice die shortly after birth, we performed stereotaxic injections of lentiviruses encoding two independent shRNAs against Nurr1 (shNurr1-1 and shNurr1-2) or control shRNA (shCtrl) into the SN of adult wild-type mice (Fig S2A). shNurr1-1 and -2 efficiently and specifically reduced Nurr1 mRNA and protein expression in the
