Novel Agents that act in Steroid-like signaling pathways in Medicine and Agriculture
BACKGROUND: The END-2 protein of the nematode Caenorhabditis elegans is a member of the nuclear hormone receptor family. Classically, nuclear hormone receptors are thought to be localized in the cytoplasm and nucleus of the cell. Steroids or steroid-like molecules, such as retinoids, diffuse across membranes, bind to the appropriate nuclear hormone receptors and cause them to become transcriptional activators.
DESCRIPTION: UC researchers have developed new evidence showing that steroid receptors may function at the cell surface. END-2 is the first nuclear hormone receptor to be found primarily at the plasma membrane. END-2 and the components of this signaling pathway at the cell surface, will enable discovery of drugs that specifically target either the membrane interactions or the nuclear function of nuclear hormone receptors, leading to new therapeutic agents replacing steroid drugs in current use. Newly developed steroid drugs would be targeted more specifically, and might not be plagued with the negative side effects common to current steroid drugs. In addition, END-2 may mediate the signaling events that lead to formation of an alternative form of nematodes, which is required for infectivity and long-term survival. This finding may, therefore, provide a means for discovering new anti-helminth agents effective against pathogenic and parasitic nematodes of plants and animals.
* Development of new alternatives to steroid treatment. END-2 and its family members may lead to generation of new therapeutics that modulate steroid signaling pathways either positively or negatively. Such therapeutics could be useful for treating human diseases. Identification of the components of the END-2 family signaling pathway, and those that bind to END-2 at the cell membrane, can provide many new drug targets. As these drugs would be designed to modify only the membrane function of the nuclear hormone receptors, they would potentially have fewer side effects than the steroid-like drugs in use today.
* Generation of new inducible systems for use in biotechnology. An inducible protein expression system similar to the ecdysone inducible promoter system can be generated to drive gene expression using END-2. This could provide a useful tool for research labs where expression of a protein of interest needs to be tightly regulated and membrane-associated.
* Nematocidal Agents. As the potential receptor for the molecule that triggers formation of an alternative developmental form that allows parasitic nematodes to invade their hosts, END-2 could be used to develop agonists and antagonists that could specifically block the normal infectious life cycle of nematodes.
US 7,150,971 [MORE INFO
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