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Submitted on January 5, 2006
Accepted on July 24, 2006
Opposing Activities Protect Against Age Onset Proteotoxicity
Ehud Cohen 1, Jan Bieschke 2, Rhonda M. Perciavalle 1, Jeffery W. Kelly 2, Andrew Dillin 1*
1 Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA. 2 Department of Chemistry and The Skaggs Institute of Chemical Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
* To whom correspondence should be addressed.
Andrew Dillin , E-mail: dillin{at}salk.edu
Aberrant protein aggregation is a common feature of late-onsetneurodegenerative diseases, including Alzheimer disease (AD)which is associated with the misassembly of the A1-42 peptide.Aggregation-mediated A1-42 toxicity was reduced in C. eleganswhen aging was slowed by decreased insulin/insulin growth factor(IGF)-1-like signaling (IIS). The downstream transcription factors,heat shock factor-1 (HSF-1) and DAF-16 regulate opposing disaggregationand aggregation activities to promote cellular survival in responseto constitutive toxic protein aggregation. Because the IIS pathwayis central to the regulation of longevity and youthfulness inworms, flies and mammals, these results suggest a mechanisticlink between the aging process and aggregation-mediated proteotoxicity.
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[DOI: 10.1126/stke.3532006tw326] |Abstract »
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1-42 peptide. Aggregation-mediated A
