The Tale of Two Proteins
Delineating the role of the cellular prion protein as a potential mediator for α-synuclein strain propagation in mice
Raphaella So knows her research into two proteins involved in Parkinson’s disease won’t lead to a new therapy in time to save her grandfather from the ravages of the illness.
Shu Shan Chang was diagnosed with Parkinson’s nearly 20 years ago and has been using a wheelchair for the last 11 years.
“Realistically, moving from [animal] research to clinical drug research takes a long time,” says So, a neuroscientist and PhD student at the University of Toronto.
But So – who is investigating the interaction between the cellular prion protein and a second protein called alpha-synuclein – hopes her work will ensure that one day, other people won’t suffer the way her grandfather has.
“Without the work in the lab, there would be no new treatments downstream,” she says.
“If we can block the interaction between alpha-synuclein clumps and the prion protein, or we can lower the amount of cellular prion protein that is expressed in the human brain, then the disease would be slower. People would be looking at a longer timeline … or they might not get worse at all.”
Clumps of alpha-synuclein are found in the brain cells of people with Parkinson’s. These clumps eventually kill the cells that produce dopamine, the chemical messenger in the brain that controls movement.
So believes the cellular prion protein acts as a gatekeeper for alpha-synuclein, regulating how much of it enters brain cells, including the ones that produce dopamine. The amount of alpha-synuclein the prion protein lets in could influence how quickly Parkinson’s progresses.
So compares animal models engineered without the cellular prion protein to models that do have the prion protein.
She wants to understand if the presence of the prion protein changes the shape of the alpha-synuclein clumps, and if those shapes produce different types of symptoms and diseases, such as Parkinson’s and multiple system atrophy. Unlike Parkinson’s disease, which people can live with for decades, those diagnosed with multiple system atrophy see their symptoms worsen more quickly and die sooner.
“Trying to understand alpha-synuclein from a biochemical approach will benefit research into many different diseases that feature this protein,” So says.
If So can prove that the cellular prion protein is key to regulating the shape of the clumps within dopamine cells, and if those shapes result in different diseases, she will have identified it as a possible drug target for researchers trying to prevent or slow the progression of Parkinson’s. Blocking the prion protein so that it can’t interact with alpha-synuclein, for example, could change the Parkinson’s picture.
So, who grew up in Hong Kong, Toronto and Bethesda, MD, was hooked on research during an internship at a cancer lab the National Institutes of Health in Maryland.
“That one life-changing experience in high school really geared me towards biological research,” she says.
How your support made this research project possible
So encourages donors to invest in basic research, like the type of investigations she conducts.
“With everything that ends up being a drug, there is a long history of research before that. If you don’t know exactly what is happening in cells, you can’t improve the current treatments.”
On a pragmatic scale, the type of research So does is “very expensive,” she says. “Having support from Parkinson Canada will help us not have to worry about feeding me so much, so we can feed my research. Money equals experiments being done.” The funding means that her work is not limited by “being too poor to buy a better re-agent or something that will make my work more effective,” she says.Donate to fund more research projects