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Science 15 February 2008:
Vol. 319. no. 5865, pp. 916 - 919
DOI: 10.1126/science.1141448
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Review

Adapting Proteostasis for Disease Intervention

William E. Balch,1 Richard I. Morimoto,2 Andrew Dillin,3 Jeffery W. Kelly4*

The protein components of eukaryotic cells face acute and chronic challenges to their integrity. Eukaryotic protein homeostasis, or proteostasis, enables healthy cell and organismal development and aging and protects against disease. Here, we describe the proteostasis network, a set of interacting activities that maintain the health of proteome and the organism. Deficiencies in proteostasis lead to many metabolic, oncological, neurodegenerative, and cardiovascular disorders. Small-molecule or biological proteostasis regulators that manipulate the concentration, conformation, quaternary structure, and/or the location of protein(s) have the potential to ameliorate some of the most challenging diseases of our era.

1 Department of Cell Biology and the Institute for Childhood and Neglected Diseases, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
2 Department of Biochemistry, Molecular Biology, and Cell Biology, Rice Institute for Biomedical Research, Northwestern University, 2205 Tech Drive, Hogan 2-100, Evanston, IL 60208–3500, USA.
3 Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
4 The Skaggs Institute for Chemical Biology and the Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

* To whom correspondence should be addressed. E-mail: jkelly{at}scripps.edu

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