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多发性硬化症的蛋白质组学:定义病理生理学和识别(早期)生物标志物所固有的问题。

Proteomics of Multiple Sclerosis: Inherent Issues in Defining the Pathoetiology and Identifying (Early) Biomarkers.

机构信息

School of Medicine, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia.

Department of Physiology & Pharmacology, College of Veterinary Medicine, University of Diyala, Baqubah 32001, Diyala, Iraq.

出版信息

Int J Mol Sci. 2021 Jul 9;22(14):7377. doi: 10.3390/ijms22147377.

Abstract

Multiple Sclerosis (MS) is a demyelinating disease of the human central nervous system having an unconfirmed pathoetiology. Although animal models are used to mimic the pathology and clinical symptoms, no single model successfully replicates the full complexity of MS from its initial clinical identification through disease progression. Most importantly, a lack of preclinical biomarkers is hampering the earliest possible diagnosis and treatment. Notably, the development of rationally targeted therapeutics enabling pre-emptive treatment to halt the disease is also delayed without such biomarkers. Using literature mining and bioinformatic analyses, this review assessed the available proteomic studies of MS patients and animal models to discern (1) whether the models effectively mimic MS; and (2) whether reasonable biomarker candidates have been identified. The implication and necessity of assessing proteoforms and the critical importance of this to identifying rational biomarkers are discussed. Moreover, the challenges of using different proteomic analytical approaches and biological samples are also addressed.

摘要

多发性硬化症(MS)是一种人类中枢神经系统脱髓鞘疾病,其发病机制尚未得到证实。尽管使用动物模型来模拟其病理学和临床症状,但没有任何单一模型能够成功复制从最初临床诊断到疾病进展的 MS 的全部复杂性。最重要的是,缺乏临床前生物标志物阻碍了尽可能早地进行诊断和治疗。值得注意的是,如果没有这些生物标志物,那么合理靶向治疗药物的开发也会延迟,无法进行先发制人的治疗以阻止疾病的发生。本综述通过文献挖掘和生物信息学分析,评估了多发性硬化症患者和动物模型的现有蛋白质组学研究,以辨别:(1)这些模型是否能有效地模拟多发性硬化症;以及(2)是否已经确定了合理的生物标志物候选物。本文还讨论了评估蛋白质异构体的意义和必要性,以及这对识别合理生物标志物的重要性。此外,还讨论了使用不同蛋白质组学分析方法和生物样本所面临的挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/261c/8306353/ddc67c5b54f2/ijms-22-07377-g001.jpg

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