SCREENING SYSTEM FOR ANTIAPOPTOSIS THERAPEUTICS

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The objective is to provide an assay for the screening of compounds that prevent apoptotic cell death. The product and method developed would be used by pharmaceutical companies for use in screening of their compounds to identify drugs for use in treatments for Parkinson's disease and other neurodegenerative disorders. Homodimer and heterodimer formation between members of the Bc1-2 family of proteins promote or prevent cell death. The specific aim is to produce a non-toxic assay in which disruption of dimer formation between the Bc1-2 family members is quantitated employing the innovative use of interactions between recombinant proteins. Drugs that block dimer formation are good candidates for modulation of apoptosis. The goal of Phase I is to develop the assay using Bax homodimer formation and to determine the optimal conditions for the assay under controlled conditions prior to a pilot testing of candidate drugs. During Phase II, the assay will be adapted for high throughput in robotic automatic screening systems and the system will be expanded to include the other Bc1-2 family members.