Nuclear receptor gene Nurr1 in dopamine neuron development and degeneration associated with Parkinson's disease

Parkinson disease (PD) is the second most common neurodegenerative disease in adults mainly manifesting with movement disorder symptoms. The loss of dopamine (DA) neurons in the substantia nigra (SN) is the pathological hallmark of PD. Although many PD related genes and environmental factors have been identified, the mechanisms underlying the loss of DA neurons in PD are still poorly understood. Previously we have documented that Nurr1, a gene regulating DA neuron differentiation is a risk factor for PD. We have also found that down-regulation of Nurr1 can cause DA neuron degeneration, increase α-synuclein expression, and induce glia-mediated inflammation and neuronal injury. Therefore, we conclude that Nurr1 may play an important role in the development of PD. Recently, we document that small molecules acting on Nurr1 transcription site can enhance DA neuron transmission and survival under the condition of proteasome inhibition mediated DA neuron degeneration. Currently we are evaluating Nurr1-enhancing drugs for the potential of anti-PD therapy and measuring the Nurr1 level in the CSF of PD patients to determine if change of Nurr1 level is associated with the disease course of PD.