Here, we present evidence that Nurr1 plays an essential role in both microglia and astrocytes as a signal-dependent transcriptional repressor of genes that encode pro-inflammatory neurotoxic factors. Nurr1 functions as a key component of a negative feedback loop in both microglia and astrocytes by recruiting CoREST co-repressor complexes to NF-κB target genes. CoREST complexes, in turn, mediate the turnover of NF-κB and restore activated gene expression to a basal state. Loss of Nurr1 function in extraneuronal cells of the SN results in exaggerated and prolonged inflammatory responses that accelerate the loss of dopaminergic neurons in response to LPS or overexpression of a mutant form of α-Synuclein (A30P) associated with familial PD (Kruger et. al., 1998).
