In response to extracellular and intracellular stressors, the nucleus and nuclear compartments undergo distinct molecular changes to maintain cell homeostasis. In the context of Alzheimer’s disease, misfolded proteins and various cellular stressors lead to profound structural and molecular changes at the nucleus. This review summarizes recent research on nuclear alterations in AD development, from the nuclear envelope changes to chromatin and epigenetic regulation and then to common nuclear stress responses. Finally, we provide our thoughts on the importance of understanding cell-type-specific changes and identifying upstream causal events in AD pathogenesis and highlight novel sequencing and gene perturbation technologies to address those challenges.

中文翻译：

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阿尔茨海默病的核动力学和应激反应

为响应细胞外和细胞内应激源，细胞核和核区室经历不同的分子变化以维持细胞稳态。在阿尔茨海默病的背景下，错误折叠的蛋白质和各种细胞应激源会导致细胞核发生深刻的结构和分子变化。这篇综述总结了最近关于 AD 发展中核改变的研究，从核包膜变化到染色质和表观遗传调控，再到常见的核应激反应。最后，我们就了解细胞类型特异性变化和识别 AD 发病机制中的上游因果事件的重要性提供了我们的想法，并强调了应对这些挑战的新型测序和基因扰动技术。