Mitochondrial Mechanisms of Neuronal Injury

摘要

This project is focused on understanding the mechanisms of neuronal injury in acute and chronic neurodegenerative diseases. In particular, we are interested in the role that mitochondria play in both the maintenance of neuronal viability and in the execution of neurons following injurious stimuli. Our prior studies have shown that mitochondria are an essential target for calcium overload in excitotoxic neuronal injury. We have developed a model of neuronal injury in an organotypic slice preparation that should provide insight into mitochondrial events in dopaminergic neurons. We hope that this will allow the study of mitochondrial physiology in neurons that are selectively vulnerable in Parkinson's disease. In addition, we are investigating the properties of mitochondrial trafficking in neurons, which, together with an in situ study of mitochondrial DNA replication, will start to provide an unprecedented insight into mitochondrial biogenesis, movement and turnover. We believe that an understanding of the long-term properties of mitochondria in neurons will provide information that is critical to the full appreciation of the mechanisms of neuronal injury in chronic neurodegenerative disease.