Opposing Activities Protect Against Age-Onset Proteotoxicity

• DOI: 10.1126/science.1124646
• Publication Date: 2006-08-11T00:44:58Z
• Authors: Ehud Cohen; Jan Bieschke; Rhonda M. Perciav...; Jeffery W. Kelly; Andrew Dillin
• Keywords: Proteotoxicity; HSF1; Heat shock factor; Proteostasis

Aberrant protein aggregation is a common feature of late-onset neurodegenerative diseases, including Alzheimer's disease, which associated with the misassembly Aβ 1-42 peptide. Aggregation-mediated toxicity was reduced in Caenorhabiditis elegans when aging 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 activities to promote cellular survival response constitutive toxic aggregation. Because IIS pathway central regulation longevity youthfulness worms, flies, mammals, these results suggest mechanistic link between process aggregation-mediated proteotoxicity.