ALKBH8通过氧化应激调节促进神经功能
Kohei Honda1, Hiroaki Hase1, Sayaka Tanikawa1
1Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
PNAS nexus
|March 29, 2024
概括
缺少AlkB同源8 (ALKBH8) 会损害神经功能,并在小鼠中引起氧化应激. 这项研究揭示了ALKBH8
科学领域:
- 分子生物学分子生物学
- 神经科学是一个神经科学.
- 生物化学 生物化学
背景情况:
- 转移RNA (tRNA) 修改对于蛋白质翻译和细胞功能至关重要.
- AlkB同源8 (ALKBH8) 修改了tRNA波动尿素 (U34),影响了蛋白转化.
- 在哺乳动物系统,特别是中枢神经系统中,ALKBH8在体内发挥的特定作用尚不清楚.
研究的目的:
- 阐明ALKBH8在中枢神经系统中的生物功能.
- 研究ALKBH8缺乏对神经功能和相关分子机制的影响.
主要方法:
- 使用Alkbh8-Knockout (Alkbh8-/-) 小鼠来研究ALKBH8的功能.
- 评估的tRNA修饰水平,包括5-甲氧化碳胺甲基尤里丁 (mcm5U).
- 进行行为测试 (新的物体识别,旋转杆,强迫游泳) 来评估神经功能.
- 对大脑组织 (大脑皮质,海马体) 进行了组织学分析.
- 采用omics分析来识别与氧化压力相关的蛋白质和代谢物的差异表达.
- 在神经元和质细胞中测量了线粒体膜潜力.
主要成果:
- Alkbh8-/-小鼠表现出降低的mk5U水平,在大脑中部分补偿.
- 行为测试显示Alkbh8-/-小鼠的认知功能,运动协调受损,抑郁症类行为增加.
- 组织学检查显示,大脑重量减少,大脑皮质和海马体的缺血性变化.
- 奥米克斯分析发现Alkbh8-/-小鼠大脑中氧化应激路径的失调.
- 来自Alkbh8-/-小鼠的神经元和质细胞显示线粒体膜潜能减少.
结论:
- ALKBH8在维持神经功能方面发挥着至关重要的作用.
- 缺少ALKBH8导致中枢神经系统功能障碍,可能由氧化应激介导.
- ALKBH8对于调节线粒体功能和预防神经退行至关重要.
相关概念视频
Electron Transport Chain: Complex I and II
13.2K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
13.2K
Neural Regulation
39.4K
Digestion begins with a cephalic phase that prepares the digestive system to receive food. When our brain processes visual or olfactory information about food, it triggers impulses in the cranial nerves innervating the salivary glands and stomach to prepare for food.
39.4K
The Blood-brain Barrier
47.3K
Overview
47.3K
Alzheimer's Disease: Overview
469
Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
469


