We also examined whether Nurr1 exerted neuro-protective effects in the context of overexpression of an α– Synuclein mutant (A30P) associated with familial PD by combining stereotaxic injection of shNurr1- or shCtrl-lentivirus with a lentivirus encoding mutant α –Synuclein (A30P). A30P expression alone caused weak inflammation in the SN, whereas reduction of Nurr1 expression in the context of A30P expression resulted in a dramatic increase in expression of numerous inflammatory response genes, including TNFα and IL1β, and significant loss of TH+ neurons (Fig. S3A–C and data not shown). In concert, these experiments indicate that Nurr1 limits inflammatory responses in the CNS and protects TH+ neurons from LPS- and α-Synuclein (A30P)-induced toxicity.
