Small Heat Shock Proteins Collaborate with FAIM to Prevent Accumulation of Misfolded Protein Aggregates.
Small Heat Shock Proteins Collaborate with FAIM to Prevent Accumulation of Misfolded Protein Aggregates.
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DOI：
10.3390/ijms231911841
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发表时间：
2022-10-06
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
细胞和组织持续受到环境损伤，如热休克和氧化应激，这导致细胞毒性聚集蛋白的积累。我们以前发现，Fas凋亡抑制分子（FAIM）保护细胞免受应激诱导的细胞死亡，防止异常产生的蛋白质聚集体类似的小热休克蛋白（HSP）的效果。蛋白质聚集体通常与神经退行性疾病相关，包括阿尔茨海默病（AD）。在这项研究中，我们试图确定FAIM蛋白动力学在细胞应激期间如何变化，以及FAIM如何防止淀粉样蛋白-β聚集体/原纤维的形成，这是AD的病理标志之一。在这里，我们发现，FAIM蛋白的大部分转移到洗涤剂不溶性部分响应于细胞应激。在小的热休克蛋白（sHSP）家族分子，如HSP 27，应激后也观察到类似的不溶性部分的转变。我们进一步证明，FAIM被招募到含sHSP的复合物后，细胞应激诱导。这些数据表明，FAIM可能会阻止蛋白质聚集与sHSP。事实上，我们使用体外淀粉样蛋白-β聚集模型系统观察到FAIM和HSP 27对预防蛋白质聚集的额外作用。我们的工作为FAIM、sHSP和淀粉样蛋白-β聚集之间的相互关系提供了新的见解。
Cells and tissues are continuously subject to environmental insults, such as heat shock and oxidative stress, which cause the accumulation of cytotoxic, aggregated proteins. We previously found that Fas Apoptosis Inhibitory Molecule (FAIM) protects cells from stress-induced cell death by preventing abnormal generation of protein aggregates similar to the effect of small heat shock proteins (HSPs). Protein aggregates are often associated with neurodegenerative diseases, including Alzheimer’s disease (AD). In this study, we sought to determine how FAIM protein dynamics change during cellular stress and how FAIM prevents the formation of amyloid-β aggregates/fibrils, one of the pathological hallmarks of AD. Here, we found that the majority of FAIM protein shifts to the detergent-insoluble fraction in response to cellular stress. A similar shift to the insoluble fraction was also observed in small heat shock protein (sHSP) family molecules, such as HSP27, after stress. We further demonstrate that FAIM is recruited to sHSP-containing complexes after cellular stress induction. These data suggest that FAIM might prevent protein aggregation in concert with sHSPs. In fact, we observed the additional effect of FAIM and HSP27 on the prevention of protein aggregates using an in vitro amyloid-β aggregation model system. Our work provides new insights into the interrelationships among FAIM, sHSPs, and amyloid-β aggregation.
影响因子：
5.6
作者：
Hemond, Michael;Rothstein, Thomas L.;Wagner, Gerhard
通讯作者：
Wagner, Gerhard