Source:http://linkedlifedata.com/resource/pubmed/id/19298183
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rdf:type | |
lifeskim:mentions | |
pubmed:dateCreated |
2009-6-3
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pubmed:abstractText |
Many diseases appear to be caused by the misregulation of protein maintenance. Such diseases of protein homeostasis, or "proteostasis," include loss-of-function diseases (cystic fibrosis) and gain-of-toxic-function diseases (Alzheimer's, Parkinson's, and Huntington's disease). Proteostasis is maintained by the proteostasis network, which comprises pathways that control protein synthesis, folding, trafficking, aggregation, disaggregation, and degradation. The decreased ability of the proteostasis network to cope with inherited misfolding-prone proteins, aging, and/or metabolic/environmental stress appears to trigger or exacerbate proteostasis diseases. Herein, we review recent evidence supporting the principle that proteostasis is influenced both by an adjustable proteostasis network capacity and protein folding energetics, which together determine the balance between folding efficiency, misfolding, protein degradation, and aggregation. We review how small molecules can enhance proteostasis by binding to and stabilizing specific proteins (pharmacologic chaperones) or by increasing the proteostasis network capacity (proteostasis regulators). We propose that such therapeutic strategies, including combination therapies, represent a new approach for treating a range of diverse human maladies.
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pubmed:grant |
http://linkedlifedata.com/resource/pubmed/grant/AG 018917,
http://linkedlifedata.com/resource/pubmed/grant/AG 026647,
http://linkedlifedata.com/resource/pubmed/grant/AG 031097,
http://linkedlifedata.com/resource/pubmed/grant/DK 046335,
http://linkedlifedata.com/resource/pubmed/grant/DK 05187,
http://linkedlifedata.com/resource/pubmed/grant/DK 07529,
http://linkedlifedata.com/resource/pubmed/grant/GM 033301,
http://linkedlifedata.com/resource/pubmed/grant/GM 038109,
http://linkedlifedata.com/resource/pubmed/grant/GM 042336,
http://linkedlifedata.com/resource/pubmed/grant/GM 081192,
http://linkedlifedata.com/resource/pubmed/grant/HL 079442,
http://linkedlifedata.com/resource/pubmed/grant/NS 047331,
http://linkedlifedata.com/resource/pubmed/grant/R01 GM042336-21
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:issn |
1545-4509
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
78
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
959-91
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pubmed:dateRevised |
2010-12-3
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pubmed:meshHeading |
pubmed-meshheading:19298183-Animals,
pubmed-meshheading:19298183-Brain Diseases,
pubmed-meshheading:19298183-Cystic Fibrosis,
pubmed-meshheading:19298183-Humans,
pubmed-meshheading:19298183-Molecular Chaperones,
pubmed-meshheading:19298183-Protein Conformation,
pubmed-meshheading:19298183-Protein Folding,
pubmed-meshheading:19298183-Protein Stability,
pubmed-meshheading:19298183-Proteins
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pubmed:year |
2009
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pubmed:articleTitle |
Biological and chemical approaches to diseases of proteostasis deficiency.
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pubmed:affiliation |
Departments of Chemistry and Molecular and Experimental Medicine and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. epowers@scripps.edu
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pubmed:publicationType |
Journal Article,
Review,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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