Studying Alzheimer's at a molecular level to find a cure

Friday, April 6, 2018

eye lens of a microscope

Waterloo scientist hopes to support drug development that blocks toxic plaques found in the brains of people with Alzheimer’s disease.

A lack of understanding of Alzheimer’s disease at the molecular level is one of the biggest obstacles to finding a cure, says a Waterloo researcher.

Zoya LeonenkoZoya Leonenko, a professor in the Department of Biology and the Department of Physics and Astronomy, is leading nanoscale biophysics research with the hope her team’s work will one day be used by the pharmaceutical industry to develop new strategies for the prevention and cure of Alzheimer’s disease.

Leonenko is using advanced biophysics and nanotechnology methods with promising preliminary results. The ultimate goal is to develop preventive strategies using molecules such as melatonin and novel amyloid-inhibitor drugs that work at the single-molecule level.

“As a nervous system disorder that leads to progressive dementia, personality changes and death, Alzheimer’s is a devastating disease that affects so many people and families,” Leonenko says.

Toxic molecules that grow into plaques in the brain

“Without understanding the science of it, we cannot develop any drug or cure. That’s why I think this research is extremely important. Once we understand what’s going on a single molecular level, then maybe we can propose how to cure this. Without this understanding, we are lost.”

As Leonenko explains, amyloid plaques found in the Alzheimer’s-affected brain are composed of large amyloid deposits, which grow from smaller amyloid aggregates known as oligomers. These are toxic to neuronal cells and cause cell death.

Drugs that can block the formation of these toxic oligomers may help to overcome the disease.

“Discovery of the best compound that inhibits oligomer formation may lead to a major breakthrough in drug development,” Leonenko says. “This will improve the health of our aging population and will have significant economic and societal impacts.”

Leonenko and her collaborators, Professors Arvi Rauk and Michael Beazely are working together to develop novel synthetic peptide inhibitors combining theoretical, molecular and cellular approaches to achieve a “rational design“ of potential drug candidates for Alzheimer’s disease. 

The inhibitor molecular structures were designed by computer simulations, tested experimentally on a single molecule level and recently in cellular models.

“We tested a number of compounds experimentally and have exciting preliminary data, showing great potential of these inhibitors to prevent amyloid toxicity in neuronal cells,” Leonenko says. “We propose more detailed work to test a larger library of theoretically proposed compounds in order to produce lead drug candidates.

Leonenko describes her team as a very talented, devoted and skilled group of students, working in a great interdisciplinary collaboration with the laboratories of Professors Rauk and Beazely.

“We are doing quite novel research and testing novel hypotheses that are not widely accepted in the beginning,” she says. “But the University of Waterloo is unique. It is very supportive and very accepting of new hypotheses. It has a very good platform centred on technology and engineering, and a network for aging research that provides great support.