Molecular Mechanisms of Dopamine Receptor Mediated Neuroprotection
Abstract
Exposure to specific neurotoxins can cause Parkinson's disease by killing dopaminergic neurons. These neurotoxins can cause neuronal loss by inducing apoptosis in which cell death results from sequential signalling events leading from the inducer of apoptosis to the ultimate execution of the cellular changes characteristic of this process. Evidence from our laboratory and others suggest that activation of dopamine receptors can oppose the induction of apoptosis in dopamine neurons. By integrating molecular biological, pharmacological, cell biological and physiological approaches, the points of intersection of the neurotoxin-activated pathways mediating cell death and the dopamine receptor- mediated pathways that promote survival will be investigated. The locus at which dopamine receptor activation interferes with the concatenated events mediating neurotoxin- initiated apoptosis will be determined. The sequence of events leading from activation of a specific dopamine receptor to modulation of apoptosis will be investigated. This work will identify specific molecular targets for drugs that oppose neurotoxin-mediated cell loss. The results of these studies can facilitate the development of effective, rational interventions for Parkinson's disease resulting from neurotoxin exposure. Accomplishments include establishing real-time PCR and developing and testing microarray technology for these paradigms.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2000
- Accession Number
- ADA383926
Entities
People
- Stuart C. Sealfon
Organizations
- Icahn School of Medicine at Mount Sinai