相关实验视频

Updated: May 30, 2025

Treating SCA1 Mice with Water-Soluble Compounds to Non-Specifically Boost Mitochondrial Function

Treating SCA1 Mice with Water-Soluble Compounds to Non-Specifically Boost Mitochondrial Function

Published on: January 22, 2017

缺氧诱导因子1保护神经元免受Sarm1介导的神经退行

Paul Meraner, Adel Avetisyan, Kevin Swift

bioRxiv : the preprint server for biology

|January 27, 2025

概括

缺氧通过HIF-1抑制Sarm1驱动的神经退行. 稳定性缺氧诱导因子1 (HIF-1) 防止NAD+损失,保护神经元免受Sarm1-介导的损伤.

科学领域:

神经科学是一个神经科学.
分子生物学分子生物学
遗传学是一个遗传学.

背景情况:

酶Sarm1 (NAD+酶) 是神经退行的一个关键驱动因素.
对Sarm1活动的调节还不太清楚.
在正常氧气条件下,VHL蛋白向低氧诱导因子1 (HIF-1) 降解.

研究的目的:

研究Sarm1活动的调节,并确定潜在的神经保护机制.
探索VHL和HIF-1在Sarm1-介导的神经退行症中的作用.

主要方法:

通过CRISPR/Cas9查,识别抑制Sarm1-介导退化的基因.
消耗VHL和其他HIF-1降解因子.
在哺乳动物和果虫模型中表达非泛化HIF-1变体.
评估NAD+水平和神经保护.

主要成果:

失去VHL抑制了Sarm1-介导的细胞退化.
耗尽VHL或HIF-1降解因子会产生神经保护作用.
稳定HIF-1防止了由Sarm1激活引起的急剧NAD+损失.
神经保护需要HIF-1DNA结合,并导致广泛的基因表达变化.

结论:

缺氧通过HIF-1-介导的转录性变化抑制Sarm1的活性.
稳定的HIF-1使神经元对Sarm1-介导的神经退行变化不那么敏感.
这一途径代表了神经退行性疾病的潜在治疗点.

更多相关视频

Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions

Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions

Published on: August 2, 2018

Quantification of Neurovascular Protection Following Repetitive Hypoxic Preconditioning and Transient Middle Cerebral Artery Occlusion in Mice

Quantification of Neurovascular Protection Following Repetitive Hypoxic Preconditioning and Transient Middle Cerebral Artery Occlusion in Mice

Published on: May 4, 2015

相关概念视频

The Blood-brain Barrier

The Blood-brain Barrier

Regulation of Angiogenesis and Blood Supply

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...