Molecular Analysis of Neurotoxin-Induced Apoptosis

摘要

Apoptosis is a cell-suicide process that is required for the normal development of the nervous system, but that can be aberrantly activated in neurodegenerative diseases and following exposure to neurotoxins. The intracellular pathways by which these different physiological and pathophysiological stmuli cause neuronal death has not been characterized. In our original application we proposed the hypothesis that certain components of the signaling pathways activated by different apoptotic stimuli might be shared. four of these molecules had been implicated in the regulation of neuronal survival. In a request for supplemental funding that was submitted in 2001, we had proposed to extend our investigation to another well studied apoptosis-regulatory molecule - the serine-threonine kinase, Akt. In 2002, we submitted a statement of modification of work as part of our annual report. In 2003, we submitted another request for supplemental funding. The funds were to be used to study a novel and exciting chemical compound called GW6074, which we found had neuroprotective properties. Finally, in 2004 we were provided with yet another supplement to study the mechanism of action of GW5074 and examine whether this compound could prevent neurodegeneration and improve behavioral outcome in an in an animal model of Parkinson's disease.