乙-CoA碳氧酶的激活会破坏铁的稳态,从而驱动铁亡
Ziqi Han1, Shuangyu Han1, Xiaoyan Fang1
1Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, China.
Free radical biology & medicine
|May 31, 2025
概括
乙-CoA碳氧酶 (ACC) 破坏铁平衡,导致阻塞性睡眠呼吸暂停 (OSA) 的铁亡. 抑制ACC或使用empagliflozin通过恢复铁平衡和减少炎症来保护神经元.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 生物化学 生化学
背景情况:
- 乙-CoA核糖酶 (ACC) 是脂质生成中的一个关键酶.
- 阻塞性睡眠呼吸暂停 (OSA) 与神经退行有关,涉及脂质积累和铁失调.
- 铁亡是一种依赖于铁的细胞死亡途径,与神经退行性疾病有关.
研究的目的:
- 调查ACC在神经元铁恒温和OSA中的铁的作用.
- 探索针对ACC在OSA中神经保护的治疗潜力.
主要方法:
- 使用了阻塞性睡眠呼吸暂停 (OSA) 的小鼠模型.
- 使用的乙烯基-A碳氧化酶 (ACC) 基因淘汰 (KO) 和药理抑制.
- 评估了细胞铁代谢,溶酶体功能,铁亡标志物和微质激活.
- 研究了NFE2L2/NRF2-TFEB信号通路和empagliflozin的影响.
主要成果:
- 在OSA小鼠中,ACC脱度与神经元脂质积累和可变铁增加相关.
- ACC无活化恢复了溶酶体的完整性,并抑制了神经元铁亡.
- 在ACC-NRF2-TFEB-溶酶体路径中介铁稳态.
- 恩帕格利弗洛辛缓解了OSA诱导的神经元损伤和认知缺陷.
- 抑制神经元ACC降低了微质激活和神经元损伤.
结论:
- ACC在破坏铁平衡和促进神经退行症中的铁亡中发挥着关键作用.
- 向ACC为OSA和相关的神经退行性疾病提供了潜在的治疗策略.
- 这些发现突出显示了神经元健康中的脂质信号传递和铁代谢之间的联系.
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