Finding a Way to Enhance the Survival of Dopamine Brain Cells
Dopamine is found in brain cells. The death of these cells leads to the hallmark movement symptoms of Parkinson’s disease (PD) — including tremor, rigidity and issues with balance. Nitya Subrahmanian, PhD, of the University of Florida, a Parkinson’s Foundation Center of Excellence, received a Parkinson’s Foundation Launch Award to test if boosting mitochondrial function can help dopamine cells in the brain survive.
Parkinson’s movement symptoms are driven by a severe loss of a type of brain cell (called neurons) that makes the chemical dopamine. By the time a person is diagnosed with Parkinson’s, about half of their dopamine cells have already died. This loss continues over time and unfortunately, there are no medications that can preserve the existing dopamine neurons or reverse the disease. To improve quality of life, current treatments enhance dopamine levels and reduce movement symptoms.
Mitochondria are tiny compartments within the cell that are involved in energy production. Up to millions of mitochondria fuel each brain cell. Without enough healthy mitochondria, cells may not make enough energy to support brain function, leading to disease.
Complex I is an enzyme in the mitochondria that contributes to this energy generation. The enzyme does not work correctly in the brains of people with Parkinson’s.
Matthew LaVoie, PhD, at the University of Florida, recently discovered that a new chaperone (a protein that assists in the folding of other proteins) can increase mitochondrial energy levels. Dr. Subrahmanian, under the mentorship of Drs. LaVoie and Benoit Giasson, will study whether this protein can help dopamine brain cells survive in models of Parkinson’s.
Another trait of sick cells in Parkinson’s is the buildup of a toxic protein called alpha-synuclein, which causes the formation of Lewy bodies in the brain. Dr. Subrahmanian will also find out whether this mitochondrial chaperone can protect dopamine neurons from the toxic alpha-synuclein.
To answer these questions, Dr. Subrahmanian will engineer stem cells to create excess amounts of the mitochondrial protein. Stem cells are capable of multiplying and have the potential to form any type of neuron. First, Dr. Subrahmanian will guide them to become the dopamine brain cells typically lost in Parkinson’s. Then she will evaluate the protection that comes from the improved mitochondrial function. She will also use a similar approach in a mouse model.
“Our findings can help drive the development of new Parkinson’s therapies by enhancing mitochondrial function. These research efforts could lead to a profound paradigm shift, with the potential to elevate the treatment from palliative care to cure,” she said.
Of her Parkinson’s Foundation grant award, Dr. Subrahmanian said, “I am sincerely grateful to the Parkinson’s Foundation for specially designing the Launch award for young aspiring researchers like me. This award provides financial support beyond two years of mentored research. It will play a vital role in achieving my long-term career goal of becoming an independent investigator in academia.”
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