Role of Pink1 in Parkinson’s Disease
2005 Seed Grant
Xiaoxi Zhuang, Ph.D.
The University of Chicago
Parkinson’s disease. (PD) is known to be caused by degeneration of midbrain dopamine neurons. One central question in Parkinson’s disease research is what causes dopamine neuron degeneration. Both environmental (for example, toxins in the environment) and genetic factors (for example PD linked genes) contribute to Parkinson’s disease. Certain mutations in PINK1 (PTEN induced kinase) were recently identified to cause PD. PINKI is localized in mitochondria. This localization is especially relevant to PD since mitochondria dysfunction is implicated in PD, especially in PD caused by environmental toxins. Mapping out biochemical pathways that link PINKI mutations to dopamine neuron degeneration may reveal common pathways that are shared byParkinson’s disease caused by different genetic and environmental factors. Since Pll-Kl-linked PD is recessive, suggesting that such a condition may be caused by PINKI deficiency. In. order to model in vivo such a condition and to elucidate biochemical pathways leading to dopamine neuron degeneration, we have generated mice with PINKI deficiency. We propose to examine their motor behavior and dopamine system pathology in order to determine whether they represent good animal models of PD. These studies not only are important for understanding the cause of dopamine neuron degenerating in Parkinson’s disease, for finding new targets for therapeutic interventions” but are also important for providing animal models to test new drugs and therapeutic approaches.
Parkinson’s disease affects more than 1.5 million people in the United States alone. This number is expected to increase with our aging population. Until now, the cause of dopamine neuron degeneration in Parkinson’s disease is still far from clear and there are no therapeutic interventions that call prevent dopamine neurons from degenerating in Parkinson’s disease. The proposed studies not only are important for understanding the cause of dopamine neuron degenerating in Parkinson’s disease, for finding new targets for therapeutic interventions, but are also important for providing animal models to test new drugs and therapeutic approaches.