血红蛋白作为伪氧酶和与氧化压力相关的疾病的药物标
Woojin Won1, Elijah Hwejin Lee2,3, Lizaveta Gotina2,3
1Center for Cognition and Sociality, Institute for Basic Science (IBS), Daejeon, Republic of Korea.
Signal transduction and targeted therapy
|August 22, 2025
概括
大脑细胞中的血红蛋白通过分解过氧化来对抗氧化压力. 一种新的药物KDS12025增强了这种保护功能, 提供了神经退行性疾病的新疗法.
科学领域:
- 神经科学
- 生物化学
- 药理学
背景情况:
- 血红蛋白 (Hb) 主要用于运输氧气,但其在大脑内的功能,特别是星球细胞和神经元,尚不清楚.
- 过氧化 (H2O2) 水平升高会导致阿尔茨海默病,帕金森病和衰老等疾病的氧化应激和神经退行.
- 在神经退行性疾病中,星细胞Hb水平下降,从而加剧氧化损伤.
研究的目的:
- 研究Hb在脑细胞中的作用及其在神经退行过程中的参与.
- 开发和评估一种用于缓解大脑氧化应激的新疗法KDS12025.
- 探索Hb作为神经退行性疾病的潜在治疗点.
主要方法:
- 在海马和黑质星细胞和多巴胺神经元中鉴定和定位Hb.
- 开发KDS12025,一种可通过血脑屏障的小分子,旨在增强Hb的伪氧化酶活性.
- 在细胞和动物模型中评估KDS12025对H2O2水平,星,Hb正常化和神经保护的影响,包括阿尔茨海默病,帕金森病,肌缩侧面硬化和衰老.
- 对Hb进行基因沉默,以确认其对KDS12025的有效性是必要的.
主要成果:
- 在细胞质,线粒体和脑细胞核中发现Hb,作为一种伪氧化酶来分解H2O2.
- KDS12025显著增强了HB的伪氧化酶活性,降低了H2O2水平和氧化应激.
- 在各种疾病模型中,用KDS12025治疗缓解了星病,使Hb水平正常化,并预防了神经退行.
- 在严重的ALS和衰老模型中,KDS12025改善了生存和运动功能,显示出广泛的治疗潜力.
- 核中Hb的存在表明它在保护核部件方面具有新的抗氧化作用.
结论:
- 血红蛋白在神经元和星细胞抗氧化防御中起着至关重要的,以前未知的作用.
- KDS12025是一种增强Hb伪氧化酶活性的第一类治疗剂, 提供一种针对H2O2驱动的神经退行症的新策略.
- 向Hb伪氧化酶活性代表了阿尔茨海默病,帕金森病,ALS和其他与年龄相关的氧化应激障碍的有希望的治疗途径.
相关概念视频
Oxygen Transport in the Blood
3.2K
Hemoglobin (Hb) is a crucial molecule in the human body, consisting of four polypeptide chains, each bound to an iron-containing heme group. This unique structure enables hemoglobin to bind to oxygen, with each molecule capable of combining with four molecules of oxygen, leading to rapid and reversible oxygen loading. When fully loaded with oxygen, it is called oxyhemoglobin, while hemoglobin that has released oxygen is called reduced hemoglobin or deoxyhemoglobin. As hemoglobin binds oxygen,...
3.2K
Hemoglobin
4.4K
Hemoglobin is a globular protein made up of four subunits. Two of these subunits are alpha chains, and the other two are beta chains. Each subunit contains a molecule of heme, which has an iron atom and can bind to oxygen. When an oxygen molecule binds to one heme group, it changes the shape of hemoglobin, making it easier for the other heme groups to bind oxygen as well.
When all four heme groups are bound to oxygen, the resulting molecule is called oxyhemoglobin. As a result, arterial blood...
When all four heme groups are bound to oxygen, the resulting molecule is called oxyhemoglobin. As a result, arterial blood...
4.4K
Peroxisomes
14.3K
Peroxisomes are specialized organelles present in fungi, plant, and animal cells. It can vary in number, size, morphology, and activity depending on the type of tissue and the nutritional state of the cell. For example, cells with active lipid metabolism, such as adipocytes, neurons, and hepatocytes, have more peroxisomes than other cells in the body. Besides their primary role in breaking down complex organic molecules, peroxisomes can also synthesize specific macromolecules and participate in...
14.3K
Oxidation of Phenols to Quinones
3.4K
In the presence of oxidizing agents, phenols are oxidized to quinones. Quinones can be easily reduced back to phenols using mild reducing agents. The electron-donating hydroxyl group enhances the reactivity of the aromatic ring, enabling oxidation of the ring even in the absence of an α hydrogen.
o-hydroxy phenols are oxidized to o-quinones and p-hydroxy phenols to p-quinones. Such redox reactions involve the transfer of two electrons and two protons. The reversible redox...
o-hydroxy phenols are oxidized to o-quinones and p-hydroxy phenols to p-quinones. Such redox reactions involve the transfer of two electrons and two protons. The reversible redox...
3.4K
Hypoxia
1.2K
Hypoxia is a medical condition characterized by an inadequate oxygen supply to body tissues. It typically manifests as a bluish discoloration of the skin and mucosae, especially in fair-skinned individuals, when hemoglobin (Hb) saturation drops below 75%.
Types of Hypoxia
There are four primary types of hypoxia, each resulting from a different cause:
1. Anemic hypoxia: This type occurs due to insufficient oxygen delivery caused by a lack of red blood cells (RBCs) or RBCs with abnormal or...
Types of Hypoxia
There are four primary types of hypoxia, each resulting from a different cause:
1. Anemic hypoxia: This type occurs due to insufficient oxygen delivery caused by a lack of red blood cells (RBCs) or RBCs with abnormal or...
1.2K
Electron Transport Chain: Complex III and IV
8.0K
During the electron transport chain, electrons from NADH and FADH2 are first transferred to complexes I and II, respectively. These two complexes then transfer the electrons to ubiquinol, which carries them further to complex III. Complex III passes the electrons across the intermembrane space to Cyt c, which carries them further to complex IV. Complex IV donates electrons to oxygen and reduces it to water. As electrons pass through complexes I, III, and IV, the energy released aids the pumping...
8.0K


