For example, it's known that Hsp90 helps properly assemble steroid receptors in the liquid portion of a cell but receptors have to get to the cell nucleus to be functional. "We know who folds them up, but our big question is: Who takes them over there? It could be that chaperones and helpers both are important for trafficking receptors. If we can inhibit the trafficking, we can inhibit the hormone response."
Hsp90, is one of the most common of the ubiquitous heat shock proteins. These proteins are essential in the body, necessary to even digesting food. In healthy times they fold proteins properly so they'll do the right job, sometimes even delivering them where needed. During stress, heat shock proteins, such as Hsp90, work to help proteins keep proper conformation and function.
It can be bad news when they don't. When proteins start unfolding, amino acids that shouldn't get exposed can interact with other proteins to form unhealthy aggregates, such as the brain plaque that is the hallmark of Alzheimer's, Dr. Chadli says. "The role of molecular chaperones like Hsp90 is to prevent this from happening."
In the cardiovascular system Hsp90 also is a major player. Nitric oxide synthase, which makes the powerful blood vessel dilator, is dependent on it. Steroid receptors also have a role in cardiovascular health, including the protective role estrogen seems to have in women before menopause and the fact that testosterone doesn't seem to do the same for men of any age. "So how do you get both things? Receptors of these hormones need Hsp90 so we need to understand the intricacies of the Hsp90 machinery," Dr. Chadli says.
|Contact: Toni Baker|
Medical College of Georgia