Understanding where to hit Parkinson’s disease
Novel, tissue-specific, inducible, adult-onset reversible animal models for the role of mitochondria in PD
Among the busiest parts of any cell is the mitochondrion, a structure that supplies energy, transmits signals, and even coordinates a programmed death sequence for cells when they come to the end of their useful life.
Mitochondria function declines with age. Many researchers believe this problem may be the starting point — and perhaps the main problem — of the disorder.
“If you want to help treat or cure a disease, you have to first understand why that disease behaves the way it does,” says Ying Wang, a McGill University postdoctoral fellow. “My project is aimed at answering two important questions: is mitochondrial dysfunction the cause of this disease, and if we can find a way to restore that function, would it reverse the course of the disease?”
With that goal in mind, Wang has attempted to better model the way mitochondria is disrupted in Parkinson’s, in order to prove or disprove the causal role of mitochondria. She’s working with mice that have been genetically modified to create chronic stress on mitochondria, specifically in a particularly hard-working class of brain cells that are susceptible to this disease. Furthermore, she’s already discovered that a drug she gives to those mice in water can reverse the problem with the mitochondria.
“It’s a simple, elegant model,” says Wang. “It is unique because it induces adult-onset chronic loss of mitochondrial function. Furthermore, it is the first that allows us to turn the functional capacity of mitochondria off, and then back on again.” Demonstrating that this drug can reverse damage to mitochondria in these mice means focusing on mitochondria is a good potential avenue for drug discovery.
The lab of Dr. Siegfried Hekimi, where Wang earned her PhD in 2014, has been an ideal setting to carry out this work, she says.
“This lab has been working on aging and these kinds of age-dependent diseases for the last 20 years,” she says. “We have also been thinking of ways to improve mitochondrial function that could potentially benefit many age-related illnesses.”