Modulation of Rit2 expression to protect against alpha-synuclein neuropathology

Martin Levesque
Associate Professor
Laval University
Pilot Project Grant
$50,000 over 1 year

A protein called alpha-synuclein, which accumulates in clumps in the brain cells of people with Parkinson’s disease, has long been the target of researchers investigating the causes of this degenerative illness. The way alpha-synuclein interacts with other proteins is thought to be the key to how Parkinson’s progresses.

At Laval University, Associate Professor Martin Levesque concentrates on the relationship between alpha-synuclein and another protein called Rin. Levesque uses genetically modified mice models to increase the amount of Rin in the dopamine-generating brain cells.

During previous tests at the cellular level, increasing Rin decreased the amount of alpha-synuclein building up in neurons.

“Rin increases the cell’s ability to get rid of toxic proteins,” says Levesque.

Levesque and other researchers believe Parkinson’s results when the normal protein-clearing process in cells goes awry, allowing toxic amounts of alpha-synuclein to build up and kill the dopamine cells.

“We’re interested in how these dopamine-producing brain cells make their connection, and what the factors are that maintain and ensure their survival,” he says.

If Levesque and his colleagues succeed in demonstrating that increasing Rin decreases alpha-synuclein, preventing the clumps from forming and protecting neurons, they will have opened a new pathway and target for drugs.

The next step in Levesque’s research will be screening for a drug that increases Rin.

“Then we could have a neuroprotective compound against the degeneration,” he says. “The patient would take pills that would enhance the Rin activity and block the progression of the disease.”
Although there are many steps required for Levesque and his colleagues to develop a new protective drug, he believes his research is on a hopeful path.

“If we develop a drug … for a person who has just developed Parkinson’s, it would mean they would not suffer too much from the disease. That would be the dream,” he says.

Levesque began his academic career with an undergraduate degree in biology. He became a neuroscientist after becoming fascinated with brain development, and studying the connectivity of dopamine in different regions of the brain.

Today, his entire lab is dedicated to studying dopamine cells.

“There is no cure for Parkinson’s,” Levesque says. “There’s a large area of research that still has to be done to develop something that will actually block or change the progression of the disease.”