Promoting Mitochondrial Transport in Dopaminergic Neurons
Research Grant, 2017
Healthy mitochondria (powerhouses of the cell) are crucial to the survival of neurons, and poorly-functioning mitochondria are implicated in the neurodegeneration associated with Parkinson's disease (PD). The maintenance of a healthy population of mitochondria in a neuron requires the synthesis of new mitochondria, their transport to the many parts of the cell where they are needed and the removal of old and damaged mitochondria. This study focuses on mitochondrial transport and explores whether it can be improved to increase neuronal survival.
We hypothesize that certain small molecules can enter cells to stimulate mitochondrial transport.
Several small molecules will be evaluated in cultures of neurons. Mitochondria
transport will be tracked using a fluorescence microscope. In each test, 40,000
mitochondria will be tracked and their movements will be measured. Approximately
1,000 molecules will be tested in this manner to see if they can increase mitochondrial
Impact on Diagnosis/Treatment of Parkinson's disease:
The compounds identified in this screen may serve as a starting point for developing therapies that prevent cells from degenerating by increasing their ability to ship healthy mitochondria out to distant parts of the cell where they are needed.
Next Steps for Development:
For any molecules that can increase mitochondrial movement, we will determine the mechanism underlying this action. This step, called target identification, is crucial for further drug development and subsequent testing to determine if targeting mitochondrial transport can increase PD neuronal survival.
Professor at Boston Children's Hospital and Harvard Medical School
Location: Boston, Massachusetts, United States