| Abstract No.: | 309 |
| Country: | Canada |
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| Title: | MECHANISMS OF DEATH IN A MODEL OF PARKINSONS DISEASE |
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| Authors/Affiliations: | David Park
University of Ottawa, ON, Canada |
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| Content: | One of the well characterized consequences of PD is the degeneration of dopamine neurons. However, the signals which regulate dopaminergic loss is only starting to be delineated. Administration of the complex1 inhibitor MPTP in vivo leads to degeneration of dopamine neurons and terminals. Using this model, we characterized an important pathway of injury. We show that the cysteine protease calpains are activated leading to cleavage of p35 the required activator of cdk5, a kinase implicated in neuronal development. We show that this cleavage event is critical for a pathogenic activity of cdk5. Cdk5, in turn, diminishes a variety of activities required for normal neuronal health. This includes transcription factors associated with survival as well as enzymes which repair DNA and reduce oxidative stress. The specifics of these cdk5 targets will be discussed in this presentation. |
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