Scientist who spotted key role of mitochondria in Parkinson’s honored
James Surmeier led team that found loss of cell energy 'sufficient' for disease
A neuroscientist at Northwestern University in Chicago was given the 2023 Annemarie Opprecht Parkinson Award, an international honor recognizing significant contributions to Parkinson’s disease research.
James Surmeier, PhD, is a professor and chair of university’s neuroscience department, and a scientific advisor to the Michael J. Fox Foundation for Parkinson’s Research, which partly supported key work by Surmeier and his team.
The work cited in the award, published in the journal Nature in 2021, demonstrated that loss of mitochondria function in dopaminergic neurons is sufficient to cause Parkinson’s disease. Mitochondria are organelles inside cells that are necessary for energy production.
Key enzyme’s absence seen to disrupt mitochondria, nerve cell communication
Presented every three to six years by the Annemarie Opprecht-Foundation, the award includes 100,000 Swiss francs (roughly $110,500) to promote medical and medical-related research into Parkinson’s.
“This award is an honor, but it is important to remember that this was a team effort,” Surmeier said in a university press release. “The award is a recognition of the effort made by an outstanding group of Northwestern scientists and staff.”
It is commonly recognized that Parkinson’s disease is caused by the dysfunction and death of nerve cells responsible for producing dopamine — a chemical that neurons use to communicate with each other — in a brain region called the substantia nigra. This region also links the basal ganglia — a brain network that helps to control voluntary movement — with the rest of the brain.
Surmeier and his collaborators showed in their study that mitochondrial damage in dopaminergic neurons caused progressive, Parkinson’s disease-like features in mice.
Specifically, they discovered that the disruption of mitochondrial complex 1, an enzyme required for mitochondria to produce energy, led to an early loss of axonal function in these neurons — disrupting communication between the substantia nigra and other parts of the brain, particularly the striatum, a brain region also affected in Parkinson’s disease.
Axonal function refers to the role of the axon, which is the long, thread-like fiber projecting from a nerve cell. It works to transmit electrical signals, called nerve impulses, from the nerve cell body, allowing a neuron to communicate with other nerve or muscle cells.
Previously, it was thought that impaired communication between dopaminergic neurons in the substantia nigra and the striatum was responsible for Parkinson’s motor symptoms.
Modest symptoms with cell axon damage, parkinsonism with mitochondrial loss
The Northwestern researchers found that axonal damage led to modest deficits in mice’s motor skills and learning, but not to full-blown parkinsonism.
“This axonal deficit was accompanied by motor learning and fine motor deficits, but not by clear levodopa-responsive parkinsonism,” the researchers wrote.
“Although loss of dopaminergic signaling in the striatum was important, it wasn’t sufficient to cause the cardinal deficits of the disease,” Surmeier said.
The gradual appearance of key motor symptoms led to further investigations. The researchers observed that parkinsonism only emerged after the later loss of communication between dopaminergic neurons within the substantia nigra.
“We used intersectional genetics to specifically disrupt a key subunit in mitochondrial complex one, just in dopaminergic neurons. This prevented mitochondria from generating ATP – the energy currency of cells,” Surmeier said. “With this single genetic disruption, mice exhibited a progressive, levodopa-responsive Parkinsonism that closely mimicked the human disease.”
The “loss of mitochondrial function alone was sufficient,” he added.
Marking the 25th anniversary of the Annemarie Opprecht Foundation, an award of the same value also was given to two researchers in the U.K. — Michel Goedert, PhD, and Sjors Scheres, PhD, with the MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus.
Research they led, published in the Nature journal in 2022, identified a distinct structure to alpha-synuclein protein filaments in the brains of people with Parkinson’s dementia and Lewy body dementia. In Parkinson’s, alpha-synuclein clumps and is toxic to dopamine-producing nerve cells.