SKN-1 and Oxidative Stress Resistance

Description: The transcription factor SKN-1 specifies formation of the feeding and digestive system during early stages of C. elegans embryogenesis. The inventor and his colleagues have shown that in larvae and adults SKN-1 regulates the Phase 2 detoxification response, a conserved defense against oxidative stress, and that skn-1 is important for stress resistance and longevity. In addition, the investigators have found that glycogen synthase kinase-3 (GSK-3) is a regulator of SKN-1. C. elegans provides a valuable system for investigating how this detoxification mechanism functions and is regulated in the context of a whole organism, and also forms the basis for rapid screening assays for the identification of drug candidates. Clinical & Commercial Utility: The invention therefore comprises screening assays to identify compounds that can up- or down-regulate the Phase 2 detoxification system. Such assays can either measure activation of SKN-1 or can be used to identify inhibitors of regulatory molecules like GSK-3, inhibition of which would serve to activate the oxidative stress resistance pathways. Oxidative stress resistance pathways are important in a number of disease states including diabetes, atherosclerosis and HIV, and possibly also longevity and cancer prevention, and so the assays of this invention have potential utility in a number of fields.
A U.S. patent application claiming this invention has been filed. Recent research relating to this invention has been published in An et al. (2005) PNAS 102: 16275-16280, and Inoue et al. (2005) Genes Dev. 19:2278-2283.

Type of Offer: Licensing

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