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Molecular chaperones as therapeutic targets to counteract proteostasis defects
Author(s) -
Cattaneo Monica,
Dominici Roberto,
Cardano Marina,
Diaferia Giuseppe,
Rovida Ermanna,
Biunno Ida
Publication year - 2012
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22856
Subject(s) - proteostasis , biology , protein folding , epigenetics , computational biology , microbiology and biotechnology , robustness (evolution) , proteome , bioinformatics , genetics , gene
The health of cells is preserved by the levels and correct folding states of the proteome, which is generated and maintained by the proteostasis network, an integrated biological system consisting of several cytoprotective and degradative pathways. Indeed, the health conditions of the proteostasis network is a fundamental prerequisite to life as the inability to cope with the mismanagement of protein folding arising from genetic, epigenetic, and micro‐environment stress appears to trigger a whole spectrum of unrelated diseases. Here we describe the potential functional role of the proteostasis network in tumor biology and in conformational diseases debating on how the signaling branches of this biological system may be manipulated to develop more efficacious and selective therapeutic strategies. We discuss the dual strategy of these processes in modulating the folding activity of molecular chaperones in order to counteract the antithetic proteostasis deficiencies occurring in cancer and loss/gain of function diseases. Finally, we provide perspectives on how to improve the outcome of these disorders by taking advantage of proteostasis modeling. J. Cell. Physiol. 227: 1226–1234, 2012. © 2011 Wiley Periodicals, Inc.