在阻塞性睡眠呼吸暂停诱导的神经元损伤中,对NRF2驱动的抗氧化作用需要依赖TFEB的自-溶酶体通路
Junxiu Song1, Tian Wang2, Jau-Shyong Hong3
1Respiratory Department, Tianjin Medical University General Hospital, Tianjin Medical University, 300052 Tianjin, China.
Cellular signalling
|January 28, 2025
概括
阻塞性睡眠呼吸暂停 (OSA) 损害神经元TFEB,这是细胞清洁的关键调节者. 激活TFEB-依赖性通路可以防止OSA诱导的神经退行和认知衰退.
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
- 睡眠医学 睡眠医学
背景情况:
- 阻塞性睡眠呼吸暂停 (OSA) 影响全球近10亿人,可能与神经退行有关.
- 在与OSA相关的神经元氧化应激中,TFEB (转录因子EB) 是自和 lysosomal biogenesis 的主调节者,其作用在很大程度上是未知的.
研究的目的:
- 调查TFEB在神经元氧化应激和OSA造成的损伤中的作用.
- 在OSA模型中探索TFEB,自-溶酶体通路 (ALP) 激活和神经保护之间的关系.
主要方法:
- 利用OSA小鼠模型来研究神经元TFEB和NRF2表达.
- 进行了染色试验 (HO1,SOD3,ROS,GSH,8-OHdG,MDA,PI) 来评估氧化还原平衡和神经元损伤.
- 通过基因操纵 (敲击/抑制) 调查了依赖TFEB的ALP和NRF2介导的氧化应激缓解之间的相互作用.
主要成果:
- 在OSA小鼠模型中发现神经TFEB诱导被抑制.
- 激活依赖TFEB的ALP可以减少海马神经元死亡和OSA的认知障碍.
- 在OSA模型中,NRF2诱导也存在缺陷;NRF2增强恢复了氧化还原平衡并保护了神经元.
- 发现了一种新的相互作用:NRF2的抑制会损害TFEB表达和ALP,而TFEB的抑制或自细胞阻断会降低NRF2的抗氧化作用.
结论:
- TFEB-依赖的ALP在NRF2-促进的氧化还原平衡中起着至关重要的下游作用.
- 这项研究揭示了NRF2抗氧化作用和TFEB依赖ALP调节的新机制.
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