The heat shock, or cell stress, response was first identified inthe polytene chromosomes of Drosophila. This was laterrelated to the appearance of novel proteins within stressed cells,and the key signal stimulating this appearance was identified asthe presence of unfolded proteins within the cell. It is now knownthat this is a key mechanism enabling cells to survive a multitudeof physical, chemical and biological stresses.
Since the promulgation of the 'molecular chaperone'concept as a general cellular function to control the process ofcorrect protein folding, a large number of molecular chaperones andprotein folding catalysts have been identified, and it has beenrecognized that not all molecular chaperones are stress proteinsand vice versa. The discovery of molecular chaperones as foldingproteins went hand-in-hand with their recognition as potentimmunogens in microbial infection. It was subsequently shown thatadministration of molecular chaperones such as Hsp60, Hsp70 orHsp90 could inhibit experimental autoimmune diseases andcancer.
More recently evidence has accumulated to show that certainmolecular chaperones are also present on the surface of cells or inextracellular fluids. A new paradigm is emerging: at least somemolecular chaperones are secreted proteins with pro- oranti-inflammatory actions, regulating the immune response in humandiseases such as coronary heart disease, diabetes and rheumatoidarthritis. In addition to having direct effects on cells, molecularchaperones can bind peptides and present them to T cells tomodulate immune responses. This may be significant in the treatmentof cancer.
This is the first book bringing leading researchers in thisfield together to review and discuss:
* our current knowledge of cell stress response and molecularchaperones
* the changing paradigms of protein trafficking and function
* cell stress proteins as immunomodulators and pro- andanti-inflammatory signalling molecules
* the role of these proteins in various chronic diseases andtheir potential as preventative or therapeutic agents.
The Biology of Extracellular Molecular Chaperones is ofparticular interest to immunologists, cell and molecularbiologists, microbiologists and virologists, as well as clinicalresearchers working in cardiology, diabetes, rheumatoid arthritisand other inflammatory diseases.