The Role of HSP70 and Its Co-chaperones in Protein Misfolding, Aggregation and Disease - The Networking of Chaperones by Co-chaperones - page 240

Chapter 12
The Role of HSP70 and Its Co-chaperones in
Protein Misfolding, Aggregation and Disease

Emma J. Duncan, Michael E. Cheetham, J. Paul Chapple
and Jacqueline van der Spuy

Abstract Molecular chaperones and their associated co-chaperones are essential
in health and disease as they are key facilitators of protein folding, quality control
and function. In particular, the HSP70 molecular chaperone networks have been
associated with neurodegenerative diseases caused by aberrant protein folding. The
pathogenesis of these disorders usually includes the formation of deposits of mis-
folded, aggregated protein. HSP70 and its co-chaperones have been recognised as
potent modulators of inclusion formation and cell survival in cellular and animal
models of neurodegenerative disease. In has become evident that the HSP70 chap-
erone machine functions not only in folding, but also in proteasome mediated deg-
radation of neurodegenerative disease proteins. Thus, there has been a great deal
of interest in the potential manipulation of molecular chaperones as a therapeutic
approach for many neurodegenerations. Furthermore, mutations in several HSP70
co-chaperones and putative co-chaperones have been identified as causing inherited
neurodegenerative and cardiac disorders, directly linking the HSP70 chaperone sys-
tem to human disease.

Keywords HSP70 ﾷ Co-chaperone ﾷ Protein misfolding and aggregation ﾷ
Neurodegeneration