Protecting Midbrain Neurons to Delay or Treat Parkinson’s
Lindsay Mitchell De Biase, PhD, from the University of California, Los Angeles, received a Parkinson’s Foundation Stanley Fahn Junior Faculty Award to gain a better understanding of the role of central nervous system immune cells called microglia in Parkinson’s disease (PD). Ultimately, this work could lead to therapies that delay or treat Parkinson’s.
Microglial cells can shape neuron function and health and remove debris from surrounding tissue. They regulate the signaling connections between neurons (called synapses). They also regulate central nervous system inflammation. Previous research suggests structures within the cell called mitochondria may be able to regulate the function of midbrain microglia and their responses to aging.
“Many gene mutations that increase the risk for Parkinson’s are mutations in genes related to mitochondrial function,” said Dr. De Biase. “We think that some of these mutations are increasing disease risk, not only by affecting energy production within neurons but by pushing microglial into a damaging, inflammatory state.”
Dr. De Biase’s goal is to determine if manipulating the function of microglia can protect midbrain dopamine (DA) neurons, which regulate movement and play an important role in the progression of PD. Currently, there is no way to protect these brain cells.;
“Microglia are dynamic, malleable cells and could represent therapeutic targets that are highly distinct from many that have been explored thus far,” said Dr. De Biase.
Microglia are different in the midbrain compared with other brain regions, Dr. De Biase discovered. During aging, they multiply. They release inflammatory factors earlier than microglia in other brain regions. This creates early “pockets” of inflammation that are likely to interfere with synapse function and neuron health.
These findings suggest that the unique traits of midbrain microglia are key to making DA neurons more vulnerable to Parkinson’s. Discovering what makes these microglia more responsive to aging and disease holds great promise for harnessing these cells to protect DA neurons.
Using new technology, Dr. De Biase will seek to better understand the role of microglial mitochondria in a mouse model of Parkinson’s disease. The intervention strategy she develops could be used in people who are at high risk for developing the disease, to delay or prevent disease onset. In people with PD, it could be used to create a more neuroprotective environment, preserve remaining dopamine neurons, and hopefully, delay disease progression.
Dr. De Biase has taken inspiration in her work from her father, a retired physician, who at times expressed frustration about the limits to what treatments he could offer and was envious of researchers who work to advance scientific knowledge.
“I have always hoped that my research efforts can benefit human health,” Dr. De Biase said. “We clearly need both clinicians and researchers. Even if I can’t meet with patients directly in a consultation room, I am hoping that our research can go on to help numerous people out there who each have their unique stories and struggles with the disease.”
Of the Parkinson’s Foundation grant, Dr. De Biase said, “This award has been absolutely instrumental in giving us the support to pursue these studies. I am a relative newcomer to the field of Parkinson’s research. This award will help us secure additional funding to continue pushing forward in this research direction. Interacting with other researchers and individuals living with PD through the Foundation is also enormously beneficial to our efforts.”
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