Neuronal polarity defects as an underlying cause of neurological diseases.
Neurons are cells with long extensions that send information from one part of the nervous system to another. Two types of neural extensions exist: the dendrites, which receive the information and the axon, which carry the information to other parts of the nervous system. The structures responsible for neurons to transmit their information between one another are called synapses. In order for neurons to normally relay electrical signals, cellular components (such as proteins) need to be sent to the correct cellular location (axons, dendrites, or synapses) during neuron formation. In addition, in the mature nervous system, existing and newly produced cellular components need to be sent to and kept in the right location inside neurons. This process is referred to as cellular polarity. In this research proposal, Dr. Cayouette and his team suggest that the loss of cellular polarity could be a mechanism underlying multiple brain diseases, such as neurodegenerative diseases (like Alzheimer’s disease, stroke, and retinal degeneration), neuronal connectivity diseases (such as autism and schizophrenia), and brain cancer. Key to cell polarity processes are Par proteins, a family of proteins responsible for correctly segregating cellular components. The team is using innovative molecular and cellular approaches to investigate the role of these proteins in four critical neuronal events underlying multiple brain diseases: the creation of neuronal cells, the formation of connections between neurons, the transmission of information by synapses, and the maintenance of neuronal structure in the mature nervous system. Included in this analysis will be a critical test of how cellular polarity defects can affect the function of neurons involved in locomotion and vision. These studies will have a major impact on our fundamental understanding of cell polarity and have the potential to determine a common underlying cause of neuronal disruption and discover new treatments for a wide spectrum of neurological diseases.
Michel Cayouette , Institut de Recherches Cliniques de Montréal, Université de Montréal
Fred Charron, Institut de Recherches Cliniques de Montréal, Université de Montréal
Artur Kania, Institut de Recherches Cliniques de Montréal, Université de Montréal
Keith Murai, Research Institute of the McGill University Health Centre
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