Regulating the regulators

Dr. Pascale Legault
Université de Montréal
Pilot Project Grant
Funded by Parkinson Québec
$50,000 over 1 year
MicroRNA-protein network regulating alpha-synuclein

Pascale Legault vividly recalls her primary school years, when she would visit the long-term care hospital where her father worked as a medical doctor.

The people there, some of whom were undoubtedly suffering from Parkinson’s disease, had become physically debilitated to the point where they could no longer live independently. She never forgot the implications of that gloomy prospect, even though at the time she had no idea what might have caused these problems.

“Visiting his elderly patients was always a humbling experience, as I was faced with the limitations of modern medicine,” she says.

Today, as the head of the Department of Biochemistry and Molecular Medicine at Université de Montréal, Legault has a profound desire to better understand the causes of Parkinson’s disease. Thanks to her clear memory of what this condition can do to people’s lives, her work has become dedicated to transcending those frustrating medical limitations.

“The results from this research have the potential to bring the next paradigm shift in our understanding of Parkinson’s disease,” she says, referring to her ongoing study of a fundamental mechanism associated with this ailment.

Legault’s research has focused on RNA, a family of fundamental biological molecules that shape the health of all living things. A recently discovered group of these molecules, known as microRNAs, plays highly specialized roles within our body’s development and metabolism. In particular, they regulate the levels of a protein called alpha-synuclein, which is a crucial component in the neurons that make up the nervous system.

“The stage we are at now is identifying key players in regulating the microRNA levels, which are important for homeostasis and may be disruptive in Parkinson disease.”

When microRNAs fail to regulate alpha-synuclein, this protein forms clumps that kill these neurons, leading to the symptoms we associate with Parkinson’s— impaired muscle control, trouble speaking, and physical instability.

With a pilot project grant from Parkinson Canada, Legault is leading efforts to learn how specific microRNAs that regulate alpha-synuclein are themselves controlled, with the ultimate goal of determining how to preserve their regulatory abilities.

“We advance step by step,” she says, noting that this research builds on the results of her earlier investigation in this field, which Parkinson Canada funded in 2013.

“Thanks to this earlier grant, we develop technology to identify proteins that bind RNA molecules,” she says. “Now this technology is ready to be applied to discovering proteins that regulate microRNA levels, which could be the target for potential therapies.”

Above all, her original inspiration has been reinforced as she has seen some aging members of her extended family develop Parkinson’s.

“It’s bringing this project home.”