Opposing activities protect against age-onset proteotoxicity

Ehud Cohen, Jan Bieschke, Rhonda M. Perciavalle, Jeffery W. Kelly, Andrew Dillin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

714 Scopus citations

Abstract

Aberrant protein aggregation is a common feature of late-onset neurodegenerative diseases, including Alzheimer's disease, which is associated with the misassembly of the Aβ1-42 peptide. Aggregation-mediated Aβ1-42 toxicity was reduced in Caenorhabiditis elegans when aging was slowed by decreased insulin/insulin growth factor-1-like signaling (IIS). The downstream transcription factors, heat shock factor 1, and DAF-16 regulate opposing disaggregation and aggregation activities to promote cellular survival in response to constitutive toxic protein aggregation. Because the IIS pathway is central to the regulation of longevity and youthfulness in worms, flies, and mammals, these results suggest a mechanistic link between the aging process and aggregation-mediated proteotoxicity.

Original languageAmerican English
Pages (from-to)1604-1610
Number of pages7
JournalScience
Volume313
Issue number5793
DOIs
StatePublished - 15 Sep 2006
Externally publishedYes

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