Researchers at the University of Toronto have discovered a method to improve the preclinical production of important neurons that diminish in Parkinson’s disease. This discovery offers a new approach to treating a disease that currently has no cure and very few effective treatments. The researchers achieved this by using an antibody to specifically stimulate a receptor in a molecular signaling pathway, which resulted in the development of dopaminergic neurons.These neurons produce dopamine, which is an important neurotransmitter for brain health. Researchers worldwide have been trying to encourage stem cells to turn into dopaminergic neurons in order to replace those that are lost in Parkinson’s disease patients. However, they have faced difficulties in targeting particular receptors and brain regions. “We utilized synthetic antibodies that we had created earlier to aim at the Wnt signaling pathway,” stated Stephane Angers, the lead researcher of the study and director of the Donnelly Centre for Cellular and Molecular Biology. “We are able to specifically activate this pathway.””By targeting specific receptors in the pathway, we have discovered a way to guide stem cells in the midbrain to develop into neurons,” explained Angers, who also holds the Charles H. Best Chair of Medical Research at U of T and is a professor in the Leslie Dan Faculty of Pharmacy and the Temerty Faculty of Medicine. “This method of activation has not been previously investigated.” The findings of the study were recently published in the journal Development.
Parkinson’s disease, which affects over 100,000 Canadians, is the second-most common neurological disorder after Alzheimer’s. It predominantly impacts older men, leading to progressive movement impairments and causing discomfort.The connection between sleep and mental health problems has been examined in recent research. Previous studies have focused on using a GSK3 enzyme inhibitor to activate the Wnt signaling pathway. This approach impacts multiple signaling pathways involved in stem cell growth and differentiation, which can have unintended consequences on newly formed neurons and the activation of non-target cells. However, a new method has been developed to efficiently stimulate stem cell differentiation and produce neural cells in the midbrain. The method involves activating cells through the FZD5 receptor, as explained by Andy Yang, the study’s first author and a PhD student at the Donnelly Centre.The study showed that the artificially-produced neurons closely resembled natural dopaminergic neurons. Another promising result was that implanting these neurons in a rodent model with Parkinson’s disease improved the rodent’s mobility issues. Yang stated that the next step would be to continue testing the activation of the FZD5 receptor and inhibition of GSK3 in suitable models to determine which method is more effective in improving Parkinson’s disease symptoms before clinical trials. The University of Toronto Medicine by Design program supported this research., which is funded by the Canada First Research Excellence Fund and the Canadian Institutes of Health Research.
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