Parkinson’s Disease

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.

Other Grants

Lindsay M. De Biase, Ph.D., University of California Los Angeles
The role of microglial lysosomes in selective neuronal vulnerability
Synapses, the sites of signaling between neurons in the brain, play essential roles in learning, memory, and the health of neurons themselves. An enduring mystery is why some neurons are…
How the nervous system constructs internal models of the external world
As animals navigate their environments, they construct internal models of the external sensory world and use these models to guide their behavior. This ability to incorporate ongoing sensory stimuli into…
Xiaojing Gao, Ph.D., Stanford University
When Neural Circuits Meet Molecular Circuits: Quantitative Genetic Manipulation with Single-cell Consistency
Cells are the building blocks of our bodies. We get sick when the cells “misbehave”. The way modern gene therapies work is to introduce genes, fragments of DNA molecules that…
Rafiq Huda, Ph.D., Rutgers University
Conducting the orchestra of movement—functional role of striatal astrocytes in health and disease
Movement requires coordinated activity across a large brain-wide network. The striatum is a particularly important part of this circuit; it integrates motor-related information from many distinct brain regions to regulate…