阿尔茨海默病中神经元一氧化氮合酶的增加介导了自发钙信号和谷氨酸能钙反应的分化。

IF 5.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Antioxidants & redox signaling Pub Date : 2024-08-01 Epub Date: 2024-03-20 DOI:10.1089/ars.2023.0395
Rachelle Balez, Claire H Stevens, Kerstin Lenk, Simon Maksour, Kuldip Sidhu, Greg Sutherland, Lezanne Ooi
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引用次数: 0

摘要

亚硝基应激是阿尔茨海默病的一个特征,然而,导致亚硝基应激的根本原因以及一氧化氮(NO)对阿尔茨海默病神经元功能的影响在很大程度上仍是未知数。我们通过免疫组化和 Western 印迹分析了阿尔茨海默病患者和对照组的尸检组织和诱导多能干细胞(iPSC)衍生神经元中的神经元一氧化氮合酶(nNOS)蛋白水平。此外,我们还利用钙成像技术评估了调节 nNOS 功能或 NO 水平对神经元谷氨酸能信号传导的影响。我们的研究表明,在阿尔茨海默病死后组织的早期和严重受影响的脑区,nNOS 蛋白水平会升高,而在晚期和轻度受影响的脑区或认知能力正常的个体中,nNOS 蛋白水平不会升高。与对照组相比,晚期阿尔茨海默氏症(LOAD)患者的 iPSC 衍生神经元中也出现了 nNOS 增加的表型,同时亚硝酸盐(一种稳定的 NO 标记物)水平也增加了。我们观察到氮氧化物对功能的不同影响,包括加强对照组神经元的钙反应,同时失调钙信号转导,改变阿尔茨海默病神经元对谷氨酸的钙反应的幅度和动力学。药物清除 NO 或抑制 nNOS 可阻止阿尔茨海默病神经元中异常的自发钙信号传导。这些数据共同确定了阿尔茨海默病中 nNOS 蛋白的增加。功能数据表明,在非致病条件下,NO 对谷氨酸能钙信号转导的调节具有神经保护作用,而 nNOS 和 NO 的增加会导致阿尔茨海默病神经元中自发钙信号转导失调。
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Increased Neuronal Nitric Oxide Synthase in Alzheimer's Disease Mediates Spontaneous Calcium Signaling and Divergent Glutamatergic Calcium Responses.
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来源期刊
Antioxidants & redox signaling
Antioxidants & redox signaling 生物-内分泌学与代谢
CiteScore
14.10
自引率
1.50%
发文量
170
审稿时长
3-6 weeks
期刊介绍: Antioxidants & Redox Signaling (ARS) is the leading peer-reviewed journal dedicated to understanding the vital impact of oxygen and oxidation-reduction (redox) processes on human health and disease. The Journal explores key issues in genetic, pharmaceutical, and nutritional redox-based therapeutics. Cutting-edge research focuses on structural biology, stem cells, regenerative medicine, epigenetics, imaging, clinical outcomes, and preventive and therapeutic nutrition, among other areas. ARS has expanded to create two unique foci within one journal: ARS Discoveries and ARS Therapeutics. ARS Discoveries (24 issues) publishes the highest-caliber breakthroughs in basic and applied research. ARS Therapeutics (12 issues) is the first publication of its kind that will help enhance the entire field of redox biology by showcasing the potential of redox sciences to change health outcomes. ARS coverage includes: -ROS/RNS as messengers -Gaseous signal transducers -Hypoxia and tissue oxygenation -microRNA -Prokaryotic systems -Lessons from plant biology
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