Molecular Chaperones

Rebecca A. Dabbs, Amy R. Wyatt, Justin J. Yerbury, Heath Ecroyd, Mark R. Wilson, Dabbs, Rebecca A., Wyatt, Amy R., Yerbury, Justin J., Ecroyd, Heath, Wilson, Mark R.

The maintenance of the levels and correct folding state of proteins (proteostasis) is a fundamental prerequisite for life. Life has evolved complex mechanisms to maintain proteostasis and many of these that operate inside cells are now well understood. The same cannot yet be said of corresponding processes in extracellular fluids of the human body, where inappropriate protein aggregation is known to underpin many serious diseases such as Alzheimer's disease, type II diabetes and prion diseases. Recent research has uncovered a growing family of abundant extracellular chaperones in body fluids which appear to selectively bind to exposed regions of hydrophobicity on misfolded proteins to inhibit their toxicity and prevent them from aggregating to form insoluble deposits. These extracellular chaperones are also implicated in clearing the soluble, stabilized misfolded proteins from body fluids via receptor-mediated endocytosis for subsequent lysosomal degradation. Recent work also raises the possibility that extracellular chaperones may play roles in modulating the immune response. Future work will better define the in vivo functions of extracellular chaperones in proteostasis and immunology and pave the way for the development of new treatments for serious diseases.