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利用高分辨率蛋白质组学和代谢组学研究阿尔茨海默病中的新型生物标志物:微小RNA、蛋白质和代谢物。

Novel biomarkers in Alzheimer's disease using high resolution proteomics and metabolomics: miRNAS, proteins and metabolites.

作者信息

Navas-Carrillo Diana, Rivera-Caravaca José Miguel, Sampedro-Andrada Arturo, Orenes-Piñero Esteban

机构信息

Department of Surgery, Hospital HLA La Vega, Murcia, Spain.

Department of Cardiology, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain.

出版信息

Crit Rev Clin Lab Sci. 2021 May;58(3):167-179. doi: 10.1080/10408363.2020.1833298. Epub 2020 Nov 2.

Abstract

Alzheimer's disease (AD) is the most common form of dementia. It affects approximately 6% of people over the age of 65 years. It is a clinicopathological, degenerative, chronical and progressive disease that exhibits a deterioration of memory, orientation, speech and other functions. Factors contributing to the pathogenesis of the disease are the presence of extracellular amyloid deposits, called neuritic senile plaques, and fibrillary protein deposits inside neurons, known as neurofibrillary bundles, that appear mainly in the frontal and temporal lobes. AD has a long preclinical latency and is difficult to diagnose and prevent at early stages. Despite the advent of novel high-throughput technologies, it is a great challenge to identify precise biomarkers to understand the progression of the disease and the development of new treatments. In this sense, important knowledge is emerging regarding novel molecular and biological candidates with diagnostic potential, including microRNAs that have a key role in gene repression. On the other hand, proteomic approaches offer a platform for the comprehensive analysis of the whole proteome in a certain physiological time. Proteomic technology investigates protein expression directly and reveals post-translational modifications known to be determinant for many human diseases. Clinically, there is growing evidence for the role of proteomic and metabolomic technologies in AD biomarker discovery. This review discusses the role of several miRNAs identified using genomic technologies, and the importance of novel proteomic and metabolomic approaches to identify new proteins and metabolites that may be useful as biomarkers for monitoring the progression and treatment of AD.

摘要

阿尔茨海默病(AD)是最常见的痴呆形式。它影响着约6%的65岁以上人群。这是一种临床病理、退行性、慢性和进行性疾病,表现为记忆、定向、言语和其他功能的衰退。导致该疾病发病机制的因素包括细胞外淀粉样沉积物(称为神经炎性老年斑)以及神经元内的纤维状蛋白质沉积物(称为神经原纤维束),这些主要出现在额叶和颞叶。AD有很长的临床前期潜伏期,在早期阶段难以诊断和预防。尽管出现了新的高通量技术,但识别精确的生物标志物以了解疾病进展和开发新疗法仍是一项巨大挑战。从这个意义上讲,关于具有诊断潜力的新型分子和生物学候选物,包括在基因抑制中起关键作用的微小RNA,正在涌现出重要知识。另一方面,蛋白质组学方法提供了一个在特定生理时间对整个蛋白质组进行综合分析的平台。蛋白质组学技术直接研究蛋白质表达,并揭示已知对许多人类疾病起决定性作用的翻译后修饰。临床上,越来越多的证据表明蛋白质组学和代谢组学技术在AD生物标志物发现中的作用。本综述讨论了使用基因组技术鉴定的几种微小RNA的作用,以及新型蛋白质组学和代谢组学方法在识别可能用作监测AD进展和治疗的生物标志物的新蛋白质和代谢物方面的重要性。

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