Role of CDK5 in an MPTP Model of Parkinson’s Disease

 

David S. Park, Ph.D.
Ottawa Hospital Research Institute - NRI, Canada

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder where specific brain cells are damaged or killed. This disorder can be mimicked in mice with the neurotoxin MPTP which also causes symptoms in humans. In trying to understand how this damage occurs, Dr. David S. Park (University of Ottawa, Ontario) has suggested that a certain enzyme called CDK5 contributes to brain cell damage following MPTP treatment. CDK5 is a specific kinase. Kinases are emzymes which are required for a cell to function normally. In this case, however, he proposes that too much of this kinase activity is harmful to brain cells. He hopes that successful understanding of this process will lead to a clinical application of CDK inhibitors as a therapeutic for PD.

Progress Report (as of 3/2003)

Many proteins are known to have multiple purposes. One in particular, cdk5, thought to be involved with brain development, is being investigated by Dr. David S. Park at the Ottawa Hospital Research Institute (Canada) to determine its role in the neurons of the substantia nigra pars compacta (SNpc), the area most involved in PD. He and his group are attempting to use a cdk5 inhibitor (that blocks MPTP neurotoxicity) to approach the ideal of neuroprotection, that is, preventing further neuronal depletion once neurodegeneration has begun due to disease. Also part of this grant work (combined with funding from the Parkinsons Foundation of Canada) is learning if calpains (proteases activated by calcium) are a factor in activating cdk5 since they have already learned that calpain inhibition blocks MPTP toxicity as well. Dr. Park’s next step will be to submit the accumulated data to the Canadian agency for higher funding.