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阿尔茨海默病和多发性硬化症患者体内线粒体酶17β-羟类固醇脱氢酶10水平升高。

Enhanced levels of mitochondrial enzyme 17beta-hydroxysteroid dehydrogenase type 10 in patients with Alzheimer disease and multiple sclerosis.

作者信息

Kristofiková Zdena, Bocková Markéta, Hegnerová Katerina, Bartos Ales, Klaschka Jan, Rícný Jan, Rípová Daniela, Homola Jirí

机构信息

Alzheimer Disease Center, Prague Psychiatric Centre, Ustavní 91, 181 03 Prague 8, Bohnice, Czech Republic.

出版信息

Mol Biosyst. 2009 Oct;5(10):1174-9. doi: 10.1039/b904799a. Epub 2009 Jul 6.

Abstract

The multifunctional mitochondrial enzyme 17beta-hydroxysteroid dehydrogenase type 10 might play a role in the development of Alzheimer disease via its high-affinity binding to amyloid beta peptides and its neuronal over-expression. It is suggested that the cerebrospinal fluid levels of the enzyme, free or bound to amyloid beta peptides, are a potential specific biomarker of Alzheimer disease. However, mitochondrial dysfunction seems to play a role in many neurological diseases including multiple sclerosis. In this study, the specificity of changes in relation to the enzyme over-expression was evaluated using enzyme-linked immunosorbent and surface plasmon resonance sensors. The data indicated pronounced increases in the enzyme levels, specifically to 179% in multiple sclerosis and to 573% in Alzheimer disease when compared to the age-matched controls. Although the differences between both diseases were statistically significant, enzyme levels do not appear to be a highly specific biomarker of Alzheimer disease. On the other hand, enhancement in levels of the enzyme bound to amyloid beta peptides was only observed in people with Alzheimer disease, which suggests that the complex should be further considered as a possible biomarker. In patients with multiple sclerosis, our results are the first to demonstrate significant changes in enzyme expression and to suggest possible alterations in amyloid beta peptides.

摘要

多功能线粒体酶17β-羟类固醇脱氢酶10可能通过其与淀粉样β肽的高亲和力结合及其在神经元中的过度表达,在阿尔茨海默病的发展中发挥作用。有人提出,该酶在脑脊液中的水平,无论是游离的还是与淀粉样β肽结合的,都是阿尔茨海默病潜在的特异性生物标志物。然而,线粒体功能障碍似乎在包括多发性硬化症在内的许多神经疾病中都起作用。在本研究中,使用酶联免疫吸附和表面等离子体共振传感器评估了与该酶过度表达相关的变化的特异性。数据表明,与年龄匹配的对照组相比,该酶水平显著升高,在多发性硬化症中尤其升高至179%,在阿尔茨海默病中升高至573%。尽管两种疾病之间的差异具有统计学意义,但酶水平似乎并不是阿尔茨海默病的高度特异性生物标志物。另一方面,仅在阿尔茨海默病患者中观察到与淀粉样β肽结合的酶水平升高,这表明该复合物应进一步被视为一种可能的生物标志物。在多发性硬化症患者中,我们的结果首次证明了酶表达的显著变化,并提示了淀粉样β肽可能的改变。

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