Identifying & Characterizing Novel Genes That Protect Against Neuronal Necrosis in vivo

摘要: Overall Plan Summary and Rationale Project rationale. Necrosis, or" unplanned" cell death, is a major contributor to the devastating consequences of spinal cord injury (SCI), stroke, and ischemia. Blocking or delaying secondary neuronal necrosis would significantly limit debilitating consequences of injury. Detailed elaboration of the molecular mechanisms of neuronal cell death is essential for development of efficacious therapies for SCI.One of our experimental goals is to identify the molecular modulators of neuronal necrotic death using the unique advantages of the C. e/egans for genetic and molecular studies. The necrotic paradigm we study most involves initiation of cell death by hyperactivated ion channels (MEC-4 (d) and MEC10-(d)) expressed in six touch-sensory neurons and requires elevation of intracellular calcium via ER release, which activates calpain and cathepsin proteases (1). Like apoptotic cell …