Novartis Foundation Symposium 291
The Biology of Extracellular Molecular Chaperones
Chair: Peter Csermely
The heat shock, or cell stress, response was first identified in
the polytene chromosomes of "Drosophila," This was later related to
the appearance of novel proteins within stressed cells, and the key
signal stimulating this appearance was identified as the presence
of unfolded proteins within the cell. It is now known that this is
a key mechanism enabling cells to survive a multitude of physical,
chemical and biological stresses.
Since the promulgation of the 'molecular chaperone' concept as a
general cellular function to control the process of correct protein
folding, a large number of molecular chaperones and protein folding
catalysts have been identified, and it has been recognized that not
all molecular chaperones are stress proteins and vice versa. The
discovery of molecular chaperones as folding proteins went
hand-in-hand with their recognition as potent immunogens in
microbial infection. It was subsequently shown that administration
of molecular chaperones such as Hsp60, Hsp70 or Hsp90 could inhibit
experimental autoimmune diseases and cancer.
More recently evidence has accumulated to show that certain
molecular chaperones are also present on the surface of cells or in
extracellular fluids. A new paradigm is emerging: at least some
molecular chaperones are secreted proteins with pro- or
anti-inflammatory actions, regulating the immune response in human
diseases such as coronary heart disease, diabetes and rheumatoid
arthritis. In addition to having direct effects on cells, molecular
chaperones can bind peptides and present them to T cells to
modulateimmune responses. This may be significant in the treatment
of cancer.
This book brings researchers together to review and discuss: our
current knowledge of cell stress response and molecular chaperones
the changing paradigms of protein trafficking and function cell
stress proteins as immunomodulators and pro- and anti-inflammatory
signalling molecules the role of these proteins in various chronic
diseases and their potential as preventative or therapeutic
agents.
"The Biology of Extracellular Molecular Chaperones" will be of
particular interest to immunologists, cell and molecular
biologists, microbiologists and virologists, as well as clinical
researchers working in cardiology, diabetes, rheumatoid arthritis
and other inflammatory diseases.
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