Helping cells help themselves, and tackling Parkinson’s disease along the way
Understanding the molecular mechanisms dictating PINK1 auto phosphorylation
Shafqat Rasool vividly recalls his undergraduate revelation about neurodegenerative disease, the uncomfortable notion that an “expiration date” might apply to proteins, the fundamental building blocks of our health.
“I found it surprising—and a little bizarre—that proteins, which are machines that have been designed to work so perfectly, at a certain point in life can simply fail,” he says.
At the time, Rasool was pursuing his undergraduate degree in his native Pakistan, just as the structure of the key genetic protein called parkin was solved by two McGill University researchers, Jean-Francois Trempe and Kalle Gehring. That was all the inspiration he needed to find his way into Trempe’s lab in Montreal, where Rasool is now in the third year of his doctoral studies delving into the crucial role parkin plays in the development of Parkinson’s disease.
“That’s when I felt there was something new coming up in this field. That’s what really drew me to work on this particular pathway,” Rasool says.
Parkin is a protein that helps cells remove damaged components of mitochondria, the tiny structure inside cells responsible for generating energy. Parkin works alongside another gene, PINK1, which can itself malfunction. If PINK1 fails, it doesn’t do its job of removing damaged proteins and mitochondria from inside cells. They can clump up and cause the death of the brain cells that control the body’s movement, resulting in Parkinson’s disease.
Rasool emphasizes that PINK1 is crucial to maintaining mitochondrial function and quality control, something that can be lost to Parkinson’s disease. He is therefore focusing on PINK1 as a critical target for correcting the process that sets the stage for neurodegeneration. He’s exploring McGill’s extensive reference collection of small-molecule compounds, looking for other types of agents that might interact with PINK1 to correct the effect of any disease-causing mutation. The goal is to ensure that cells can respond to mitochondrial damage before it compromises them, as well as ultimately compromising an individual’s health.
Focusing on PINK1 represents a new and exciting avenue for drug treatment that could improve the lives of Parkinson’s disease patients, since this type of molecule makes a practical target for drug development.
“I think of this as an emergent field,” he says. “In the years to come we’ll really nail the importance of this pathway to discover the core of what we know Parkinson disease to be.”