EphB1 as a Novel Drug Target to Combat Pain and Addiction
Annual rept. 1 Sep 2014-31 Aug 2015
TEXAS UNIV AT DALLAS SOUTHWESTERN MEDICAL CENTER
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We have shown using knockout mice and other methods that the neuronalsynaptic receptor protein known as EphB1 is a central player in nerve injury-induced chronic neuropathic pain as well as the related pain symptoms associated with the withdrawal from opioidmorphine addiction. Our hypothesis is that EphB1 participates in pain caused by nerve damage and opioid withdrawal through the ability of its extracellular domain to form protein-protein interactions with the NR1 subunit of the NMDA receptor and inappropriately strengthen the synapses and neural circuits in the spinal cord that transmit pain signals up into the brain. Our project is to carry out high-throughput screens HTS to identify small molecular weight drug-like compounds that antagonize the EphB1NR1 protein-protein interaction. In year 1 of the project we have cloned, expressed, and purified the unique protein tools needed for the project. We have also worked to develop protein-protein interaction assays necessary for the HTS.
- Medicine and Medical Research