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Debbie McKenzie, PhD

Grant Title: Modulation of Toll-Like Receptor Signaling: Unveiling Neuroinflammation and Therapeutic Strategies in Creutzfeldt-Jakob Disease

Location: University of Alberta

Grant Year: 2024
The innate immune system provides the first line of defence against infectious agents and damaged cells and proteins. Abnormal protein aggregates, such as PrPCJD that causes CJD, trigger the innate immune system through receptors, called TLRs, on the cell surface. We have shown that activation of specific TLRs can reduce prion infections in cell cultures, leading to our hypothesis that up-regulation of these TLRs, early in an infection or disease course in animals/humans, will decrease accumulation of the misfolded prion protein, therefore, slowing or stopping disease progression. We will confirm these results from cell culture models in transgenic mouse models expressing human prion protein and infected with CJD. The long-term goal is identification of a signalling pathways with targets for prophylactic and therapeutic interventions.

About the Researcher:

Debbie McKenzie is a professor in the Department of Biological Sciences at the University of Alberta. Her research group is housed in the Centre for Prions and Protein Folding Diseases. She has been working on prion diseases since the late 1980s, primarily focusing on strains. The co-investigators, Dr. Judd Aiken and Dr. Sang-Gyun Kang, also have extensive backgrounds in prion disease; >35 years for Dr. Aiken and ~20 years for Dr. Kang. Drs. Aiken, Kang and McKenzie are, as a team, interested in the interplay between glial cells and neurons in prion disease and how modulating glial cells will impact prion replication and uptake.

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