综合应激反应的Janus框架:从恒常状态到适应不良
Dogus M Altintas1, Marina Cerqua2, Paolo M Comoglio2
1IFOM ETS-The AIRC Institute of Molecular Oncology, Milano, Italy dogus.altintas@ifom.eu.
Life science alliance
|December 29, 2025
概括
细胞激活了综合应激反应 (ISR) 来应对环境挑战. 慢性ISR在疾病中代表了一个不适应的状态,而不仅仅是长时间的防御,影响细胞命运.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 病理学 病理学 病理学
背景情况:
- 细胞激活压力通路,如综合应激反应 (ISR),在环境变化期间保持平衡.
- ISR平衡了全球蛋白质合成减少与适应因子的选择性翻译,帮助细胞存活或死亡.
- 在癌症和代谢障碍等慢性疾病中观察到持久的ISR活性.
研究的目的:
- 挑战慢性ISR仅仅是长期防御状态的观点.
- 提出持续的ISR代表了向具有独特监管机制的不适应性进行定性转变.
- 突出了解这种"Janus框架"对于疾病病理学和治疗策略的重要性.
主要方法:
- 在压力下对ISR监管的概念分析.
- 关于细胞平衡和慢性疾病中的ISR现有文献的综述.
- 为理解慢性ISR作为"Janus"状态的框架开发.
主要成果:
- 慢性ISR不仅仅是由持续时间来定义,而是通过细胞调节的定性转变来定义.
- 持续的ISR活动意味着从适应性平衡转向根深蒂固的不适应.
- 这种持续状态涉及不同的控制机制,这些控制机制积极重塑细胞命运.
结论:
- 慢性ISR的"Janus框架"区分了适应性和不适应性状态.
- 了解这种二元性对于破译疾病起源和开发有针对性的疗法至关重要.
- 未来的研究应该专注于驱动慢性ISR在病理条件下的监管机制.
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