Causes - Eric Shoubridge, Professor - Discovering the role one tiny protein plays in causing Parkinson’s disease

Eric Shoubridge, Professor
McGill University
Pilot Project Grant
$45,000 over 1 year

Role of the mitochondrial protein CHCHD2 in the Pathogenesis of Parkinson's Disease

Within our cells, tiny structures called mitochondria act as the power plants to generate the energy those cells need to survive. Although researchers don’t understand exactly why, they know that when the power plants malfunction, the disruption in the mitochondrial system can result in a range of different illnesses, including Parkinson’s disease.

At McGill University, geneticist Eric Shoubridge is studying the function of a tiny protein called CHCHD2, which lives in the space between mitochondria’s outer and inner membranes.

“It’s a little mysterious, what this protein does,” says Shoubridge, a professor in the Department of Human Genetics. “The reason we became interested is because it’s a mitochondrial protein that has been associated with Parkinson’s disease.”

Shoubridge believes mutated forms of the protein can be a rare cause of Parkinson’s disease in some individuals. Carrying the mutation can also increase the risk of developing Parkinson’s in some families. He hopes by studying the protein and its relationship to other genetic causes of Parkinson’s disease, he will better understand CHCHD2’s role. He also wants to know why, if the same biochemical system within a cell is disturbed, so many different types of disease result.

Epilepsy, heart disease, diabetes, blindness, deafness, and several kinds of neurodegenerative diseases like Parkinson’s are all associated with mutations in different kinds of mitochondrial genes.

Already, Shoubridge has learned that CHCHD2 is part of a protein complex that is associated with frontal temporal dementia and Amyotrophic Lateral Sclerosis – ALS.

“Maybe this complex has some fundamental role in maintaining mitochondrial function, and when it goes wrong, it can cause different types of neurodegenerative disorders,” he says.

By figuring out the normal function of this protein within mitochondria, Shoubridge hopes the discovery will eventually lead to knowledge about what makes the dopamine-producing brain cells that are responsible for movement susceptible to Parkinson’s disease.

If Shoubridge and his lab understand the normal function of all the proteins associated with Parkinson’s disease, such as CHCHD2, they hope eventually to provide a target for a drug or find a way to undo the process that results in the disease.

For Shoubridge, the research he conducts strikes close to home. His family is affected by Huntington’s disease, another progressive brain disorder. Huntington’s has also been linked to disruptions in the mitochondrial system within cells – so unlocking his puzzle and learning the role of CHCHD2 is particularly meaningful.

“It might allow us to mitigate the effects of the mutation in these particular cells,” he says.