Opposing activities protect against age-onset proteotoxicity
Opposing activities protect against age-onset proteotoxicity
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DOI：
10.1126/science.1124646
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发表时间：
2006-09-15
期刊：
影响因子：
56.9
通讯作者：
Dillin, Andrew
中科院分区：
文献类型：
--
作者：
Cohen, Ehud;Bieschke, Jan;Dillin, Andrew
蛋白异常聚集是迟发性神经退行性疾病的共同特征，包括阿尔茨海默病，这与Aβ(1-42)肽的组装有关。当胰岛素/胰岛素生长因子-1样信号(IIS)减少时，聚集介导的Aβ(1-42)毒性在秀丽线虫中被降低。下游转录因子热休克因子1和DAF-16调节相反的解聚和聚集活性，以促进细胞存活，以响应结构性毒性蛋白聚集。由于IIS途径是蠕虫、苍蝇和哺乳动物长寿和年轻调控的中心，这些结果表明衰老过程和聚集介导的蛋白毒性之间存在机械联系。
Aberrant protein aggregation is a common feature of late-onset neurodegenerative diseases, including Alzheimer's disease, which is associated with themisassembly of the A beta(1-42) peptide. Aggregation-mediated A beta(1-42) 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.