在自闭症谱系障碍中放松Nrf2-Keap1-BACH1轴
Andrea Vallese1, Sara Melija2, Joussef Hayek3
1Dept. of Environmental and Prevention Sciences, University of Ferrara, Ferrara, Italy; Dept. of Bioscience and Agro-Food and Environmental Technology, University of Teramo, Teramo, Italy.
Redox biology
|August 26, 2025
概括
研究人员发现Nrf2-Keap1-BACH1通路在自闭症谱系障碍 (ASD) 纤维细胞中失调. 向这种途径恢复了线粒体功能和基因表达,这表明了ASD的潜在治疗策略.
科学领域:
- 神经科学
- 细胞生物学
- 生物化学
背景情况:
- 自闭症谱系障碍 (ASD) 是一种复杂的神经发育状况,具有多因素的起源.
- 导致ASD的精确分子机制,包括细胞氧化还原平衡,尚未完全理解.
研究的目的:
- 研究自闭症患者的原发性皮肤纤维细胞中的Nrf2信号通路.
- 探索Nrf2-Keap1-BACH1轴在自闭症细胞病理中的作用.
主要方法:
- 从自闭症患者中分离和培养一次性皮肤纤维细胞.
- 通过基因和蛋白质表达分析Nrf2通路组件 (Nrf2,HO1,BACH1,Keap1).
- 评估线粒体功能 (mtROS,膜潜力) 和对硫黄 (SFN) 和黑治疗的反应.
主要成果:
- ASD纤维细胞表现出构成性Nrf2激活,HO1表达减少,BACH1核积累增加.
- 由于Keap1水平升高,ASD细胞在SFN刺激时显示Nrf2核转位受损.
- 在ASD纤维细胞中,hemin治疗使HO1表达正常化,降低了mtROS,并恢复了线粒体膜潜力.
结论:
- 在自闭症纤维细胞中发现了Nrf2-Keap1-BACH1轴的失调.
- 该轴的药理定位,特别是用血红素,显示出纠正氧化还原失衡和改善自闭症中的线粒体功能.
相关概念视频
Autism Spectrum Disorder
336
Autism spectrum disorder (ASD) is a neurodevelopmental condition marked by persistent deficits in social communication and interaction alongside restrictive and repetitive behaviors or interests. ASD is sometimes accompanied by intellectual impairment.
These core symptoms manifest differently among individuals, ranging from mild to severe. The disorder's complexity extends beyond its clinical presentation, encompassing a diverse range of biological, cognitive, and sociocultural influences.
These core symptoms manifest differently among individuals, ranging from mild to severe. The disorder's complexity extends beyond its clinical presentation, encompassing a diverse range of biological, cognitive, and sociocultural influences.
336
NF-κB-dependent Signaling Pathway
7.8K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.8K
MAPK Signaling Cascades
6.0K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
6.0K
Notch Signaling Pathway
4.4K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.4K
Enzyme-linked Receptors
79.9K
Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
79.9K
Interactions Between Signaling Pathways
6.4K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.4K


