Lichty James D, Mane Hrishikesh, Yarmey Victoria R, Miguel Adriana San
Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina, United States of America.
Joint Department of Biomedical Engineering, North Carolina State University, University of North Carolina at Chapel Hill, Raleigh, North Carolina, United States of America.
PLoS One. 2025 Apr 24;20(4):e0315810. doi: 10.1371/journal.pone.0315810. eCollection 2025.
Amyloid β (Aβ) is a peptide known for its characteristic aggregates in Alzheimer's Disease and its ability to induce a wide range of detrimental effects in various model systems. However, Aβ has also been shown to induce some beneficial effects, such as antimicrobial properties against pathogens. In this work, we explore the influence of Aβ in stress resistance in a C. elegans model of Alzheimer's Disease. We found that C. elegans that express human Aβ exhibit increased resistance to heat and anoxia, but not to oxidative stress. This beneficial effect of Aβ was driven from Aβ in neurons, where the level of induction of Aβ expression correlated with stress resistance levels. Transcriptomic analysis revealed that this selective stress resistance was mediated by the Heat Shock Protein (HSPs) family of genes. Furthermore, neuropeptide signaling was necessary for Aβ to induce stress resistance, suggesting neuroendocrine signaling plays a major role in activating organismal stress response pathways. These results highlight the potential beneficial role of Aβ in cellular function, as well as its complex effects on cellular and organismal physiology that must be considered when using C. elegans as a model for Alzheimer's Disease.
淀粉样β蛋白（Aβ）是一种因其在阿尔茨海默病中形成特征性聚集体以及在各种模型系统中引发广泛有害影响而闻名的肽。然而，Aβ也已被证明能诱导一些有益作用，比如对病原体的抗菌特性。在这项研究中，我们在阿尔茨海默病的秀丽隐杆线虫模型中探究了Aβ对压力抗性的影响。我们发现表达人Aβ的秀丽隐杆线虫对热和缺氧的抗性增强，但对氧化应激的抗性未增强。Aβ的这种有益作用由神经元中的Aβ驱动，其中Aβ表达的诱导水平与压力抗性水平相关。转录组分析表明，这种选择性压力抗性是由热休克蛋白（HSPs）基因家族介导的。此外，神经肽信号传导对于Aβ诱导压力抗性是必需的，这表明神经内分泌信号传导在激活机体压力反应途径中起主要作用。这些结果凸显了Aβ在细胞功能中的潜在有益作用，以及在将秀丽隐杆线虫用作阿尔茨海默病模型时必须考虑的其对细胞和机体生理学的复杂影响。
