Dr. Dan Gewirth, Hauptman-Woodward senior research scientist, has solved the structure of the first mammalian GRP94 protein implicated in immune diseases such as sepsis, AIDS, and certain cancers. His work is being published in Molecular Cell. The study confirms his 2001 hypothesis that this protein—GRP94—is from the same family as HSP90 proteins. As ligand-regulated chaperones, the HSP90s are key players in cellular regulation and recognition.
The HSP90 proteins can be targeted therapeutically with drugs that lead to either stimulation or inhibition. For example, inhibitors of HSP90s are being developed as therapies for diseases ranging from cancer to sepsis, and drugs that stimulate HSP90 action may be appropriate therapies for diseases involving protein folding, such as cystic fibrosis, prion diseases, and Alzheimer’s Disease. However, these are broad-spectrum inhibitors of all HSP90s, which means that unwanted side effects may occur. This work clarifies GRP94’s place in this family and could allow for the long-term development of a family of drugs that could be narrowly targeted for individual proteins.
This article was published in Drug Discovery & Development magazine: Vol. 10, No. 11, November, 2007, pp. 16.
Filed Under: Drug Discovery
