Killam Seminar Series: Novel Approaches Against Neurodegeneration

Professor, Department of Psychiatry and Neurosciences, Laval University

Novel Approaches Against Neurodegeneration: From Genetic Screens to Antibody-Based Therapeutics

Abstract: Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra, leading to motor dysfunction. While the exact cause of PD remains unclear, mitochondrial dysfunction and the accumulation of toxic protein aggregates are thought to play central roles in neuronal death. This presentation discusses two promising neuroprotective strategies. First, a CRISPR-based genetic screen identified Ligase IV (Lig4), a DNA repair protein, as critical for dopaminergic neuron survival. Notably, Lig4 knockout protected neurons from rotenone-induced toxicity in vitro and against neurodegeneration in PD mouse models. Second, the presentation highlights the use of mini-antibodies targeting α-synuclein, which prevent the spread of pathology and the onset of motor dysfunction in a PD mouse model. These findings provide new therapeutic avenues for protecting neurons and potentially modifying disease progression in PD.

Bio: Martin Lévesque is a Full Professor in the Department of Psychiatry and Neuroscience at Laval University and leads a lab at the CERVO Brain Research Centre. He earned his Ph.D. in Neurobiology from Laval University and completed postdoctoral training at the Montreal Clinical Research Institute and the National Institute for Medical Research in London. His research focuses on understanding the cellular and molecular mechanisms that regulate dopaminergic neuronal circuits. His work aims to identify molecules that guide dopaminergic axons, unravel mechanisms of neuron degeneration, and apply these findings to develop diagnostic tools, protective therapies, and cell replacement strategies to regenerate dopaminergic circuits from stem cells. Dr. Lévesque has proven expertise in Parkinson’s disease neurobiology, using both in vivo and in vitro models.

Host or Publisher The Neuro