Transcription factor Nurr1 in dopamine neuron development and neurodegeneration associated with Parkinson's disease

Abstract

Previously our laboratory and others found that Nurr1 is the most important transcription factor dictating dopamine neuron genesis, differentiation and functional maintenance. Knockout Nurr1 gene specifically causes dopamine neuron death in the substantial nigra of midbrain, where it is mostly affected in Parkinson disease (PD). Later we demonstrated that Nurr1 is closely associated with PD. We identified several Nurr1 gene defects in a few familial cases of PD, and we detected significant low levels of Nurr1 expression in the blood of PD patients. Furthermore, we documented that Nurr1 may have an interaction with PD-related protein α-synuclein and down-regulation of Nurr1 can increase α-synuclein expression in neuronal cells. Moreover, we and other laboratory recently demonstrated that Nurr1 may have a regulation effect on glia function and knock-out Nurr1 gene in microglia may cause glia-mediated neuronal injury. Therefore, we believe that Nurr1 may play a crucial role in the pathogenesis of PD.