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质谱分析作为一种定量蛋白质组学分析工具在颞叶癫痫生物标志物研究中的应用:系统综述。

Mass Spectrometry as a Quantitative Proteomic Analysis Tool for the Search for Temporal Lobe Epilepsy Biomarkers: A Systematic Review.

机构信息

Department of Medical Genetics and Clinical Neurophysiology of Postgraduate Education, V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 660022 Krasnoyarsk, Russia.

Federal State Budgetary Institution "National Medical and Surgical Center Named after N.I. Pirogov", 105203 Moscow, Russia.

出版信息

Int J Mol Sci. 2023 Jul 5;24(13):11130. doi: 10.3390/ijms241311130.

DOI:10.3390/ijms241311130
PMID:37446307
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10342111/
Abstract

Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults. Tissue reorganization at the site of the epileptogenic focus is accompanied by changes in the expression patterns of protein molecules. The study of mRNA and its corresponding proteins is crucial for understanding the pathogenesis of the disease. Protein expression profiles do not always directly correlate with the levels of their transcripts; therefore, it is protein profiling that is no less important for understanding the molecular mechanisms and biological processes of TLE. The study and annotation of proteins that are statistically significantly different in patients with TLE is an approach to search for biomarkers of this disease, various stages of its development, as well as a method for searching for specific targets for the development of a further therapeutic strategy. When writing a systematic review, the following aggregators of scientific journals were used: MDPI, PubMed, ScienceDirect, Springer, and Web of Science. Scientific articles were searched using the following keywords: "proteomic", "mass-spectrometry", "protein expression", "temporal lobe epilepsy", and "biomarkers". Publications from 2003 to the present have been analyzed. Studies of brain tissues, experimental models of epilepsy, as well as biological fluids, were analyzed. For each of the groups, aberrantly expressed proteins found in various studies were isolated. Most of the studies omitted important characteristics of the studied patients, such as: duration of illness, type and response to therapy, gender, etc. Proteins that overlap across different tissue types and different studies have been highlighted: DPYSL, SYT1, STMN1, APOE, NME1, and others. The most common biological processes for them were the positive regulation of neurofibrillary tangle assembly, the regulation of amyloid fibril formation, lipoprotein catabolic process, the positive regulation of vesicle fusion, the positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway, removal of superoxide radicals, axon extension, and the regulation of actin filament depolymerization. MS-based proteomic profiling for a relevant study must accept a number of limitations, the most important of which is the need to compare different types of neurological and, in particular, epileptic disorders. Such a criterion could increase the specificity of the search work and, in the future, lead to the discovery of biomarkers for a particular disease.

摘要

颞叶癫痫(TLE)是成人中最常见的癫痫形式。致痫灶部位的组织重组伴随着蛋白质分子表达模式的改变。研究 mRNA 及其相应蛋白质对于了解疾病的发病机制至关重要。蛋白质表达谱并不总是与其转录物的水平直接相关;因此,对于理解 TLE 的分子机制和生物学过程,蛋白质谱分析同样重要。研究和注释 TLE 患者中统计学上有显著差异的蛋白质是寻找这种疾病的生物标志物、其发展的各个阶段的一种方法,也是为进一步治疗策略的开发寻找特定靶点的一种方法。在撰写系统评价时,使用了以下科学期刊聚合器:MDPI、PubMed、ScienceDirect、Springer 和 Web of Science。使用以下关键词搜索科学文章:"蛋白质组学"、"质谱"、"蛋白质表达"、"颞叶癫痫"和"生物标志物"。分析了 2003 年至今的出版物。分析了脑组织研究、癫痫实验模型以及生物流体。从各种研究中分离出在不同研究中发现的异常表达蛋白。大多数研究都忽略了所研究患者的重要特征,例如:疾病持续时间、类型和对治疗的反应、性别等。突出了跨越不同组织类型和不同研究的重叠蛋白:DPYSL、SYT1、STMN1、APOE、NME1 等。它们最常见的生物学过程是神经原纤维缠结组装的正调控、淀粉样纤维形成的调控、脂蛋白代谢过程、囊泡融合的正调控、氧化应激诱导的内在凋亡信号通路的正调控、超氧化物自由基的去除、轴突延伸和肌动蛋白丝解聚的调控。对于相关研究的 MS 蛋白质组学分析必须接受一些限制,其中最重要的是需要比较不同类型的神经和特别是癫痫障碍。这样的标准可以提高搜索工作的特异性,并在未来发现特定疾病的生物标志物。

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