Grant: Operating Grant - Priority Announcement: ALS Canada Research Fund

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition in which motor neurons are selectively targeted. The disease is characterized by progressive muscle weakness leading to a lethal paralysis. Although major clinical symptom arise from the damage to large motoneurons, growing evidence suggest a role of other cell types from the brain, including microglia. Microglial cell are the principal immune cells of the brain. In response to variety of insults, microglia transform into activated cells involved in inflammation. Activated microglial cells and inflammation have been observed in the spinal cords of ALS patients and animal model of disease such as SOD1mutant mouse, a transgenic animal that develop progressive motor neuron disease with many pathological features resembling human disease. To date, most evidence suggest a role of inflammation and microglial cells in the late, clinical stage of disease and the role of microglia in early, preclinical stages remains unclear. Based on our preliminary evidence in this project we propose to study early changes in function/behavior of microglial cells. We propose that modulation of the early cellular microglial function is protective and may provide guidance for early therapeutic strategies in ALS.