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阿尔茨海默病蛋白质氧化的循环生物标志物:有限范围内的期望

Circulating biomarkers of protein oxidation for Alzheimer disease: expectations within limits.

作者信息

Di Domenico Fabio, Coccia Raffaella, Butterfield D Allan, Perluigi Marzia

机构信息

Department of Biochemical Sciences, Sapienza University of Rome, Rome, Italy.

出版信息

Biochim Biophys Acta. 2011 Dec;1814(12):1785-95. doi: 10.1016/j.bbapap.2011.10.001. Epub 2011 Oct 12.

Abstract

Alzheimer disease (AD), the most common dementing disorder, is a multifactorial disease with complex etiology. Among different hypotheses proposed for AD one of the most corroborated is the "oxidative stress hypothesis". Although recent studies extensively demonstrated the specific oxidative modification of selected proteins in the brain of AD patients and how their dysfunction possibly correlates with the pathology, there is still an urgent need to extend these findings to peripheral tissue. So far very few studies showed oxidative damage of proteins in peripheral tissues and current findings need to be replicated. Another limit in AD research is represented by the lack of highly specific diagnostic tools for early diagnosis. For a full screening and early diagnosis, biomarkers easily detectable in biological samples, such as blood, are needed. The search of reliable biomarkers for AD in peripheral blood is a great challenge. A few studies described a set of plasma markers that differentiated AD from controls and were shown to be useful in predicting conversion from mild cognitive impairment, which is considered a prodromal stage, to AD. We review the current state of knowledge on peripheral oxidative biomarkers for AD, including proteomics, which might be useful for early diagnosis and prognosis.

摘要

阿尔茨海默病(AD)是最常见的痴呆症,是一种病因复杂的多因素疾病。在针对AD提出的不同假说中,最有证据支持的假说是“氧化应激假说”。尽管最近的研究广泛证明了AD患者大脑中特定蛋白质的氧化修饰,以及这些蛋白质功能障碍与病理之间的可能关联,但仍迫切需要将这些发现扩展到外周组织。到目前为止,很少有研究表明外周组织中蛋白质的氧化损伤,目前的研究结果需要重复验证。AD研究的另一个局限是缺乏用于早期诊断的高度特异性诊断工具。为了进行全面筛查和早期诊断,需要在血液等生物样本中易于检测的生物标志物。在外周血中寻找可靠的AD生物标志物是一项巨大挑战。一些研究描述了一组血浆标志物,这些标志物可将AD与对照组区分开来,并被证明有助于预测从轻度认知障碍(被认为是前驱期)向AD的转化。我们综述了目前关于AD外周氧化生物标志物的知识现状,包括蛋白质组学,其可能对早期诊断和预后有用。

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