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用于帕金森病诊断和预后的血液生物标志物的鉴定:蛋白质组学研究的系统综述

Identification of blood-based biomarkers for diagnosis and prognosis of Parkinson's disease: A systematic review of proteomics studies.

作者信息

Chelliah Shalini Sundramurthi, Bhuvanendran Saatheeyavaane, Magalingam Kasthuri Bai, Kamarudin Muhamad Noor Alfarizal, Radhakrishnan Ammu Kutty

机构信息

Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Selangor Darul Ehsan 47500, Malaysia.

Brain Research Institute Monash Sunway (BRIMS), Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Selangor Darul Ehsan 47500, Malaysia.

出版信息

Ageing Res Rev. 2022 Jan;73:101514. doi: 10.1016/j.arr.2021.101514. Epub 2021 Nov 16.

Abstract

Parkinson's Disease (PD), a neurodegenerative disorder, is characterised by the loss of motor function and dopamine neurons. Therapeutic avenues remain a challenge due to lack of accuracy in early diagnosis, monitoring of disease progression and limited therapeutic options. Proteomic platforms have been utilised to discover biomarkers for numerous diseases, a tool that may benefit the diagnosis and monitoring of disease progression in PD patients. Therefore, this systematic review focuses on analysing blood-based candidate biomarkers (CB) identified via proteomics platforms for PD. This study systematically reviewed articles across six databases (EMBASE, Cochrane, Ovid Medline, Scopus, Science Direct and PubMed) published between 2010 and 2020. Of the 504 articles identified, 12 controlled-PD studies were selected for further analysis. A total of 115 candidate biomarkers (CB) were identified across selected 12-controlled studies, of which 23 CB were found to be replicable in more than two cohorts. Using the PANTHER Go-Slim classification system and STRING network, the gene function and protein interactions between biomarkers were analysed. Our analysis highlights Apolipoprotein A-I (ApoA-I), which is essential in lipid metabolism, oxidative stress, and neuroprotection demonstrates high replicability across five cohorts with consistent downregulation across four cohorts. Since ApoA-I was highly replicable across blood fractions, proteomic platforms and continents, its relationship with cholesterol, statin and oxidative stress as PD biomarker, its role in the pathogenesis of PD is discussed in this paper. The present study identified ApoA-I as a potential biomarker via proteomics analysis of PD for the early diagnosis and prediction of disease progression.

摘要

帕金森病(PD)是一种神经退行性疾病,其特征是运动功能丧失和多巴胺神经元缺失。由于早期诊断缺乏准确性、疾病进展监测困难以及治疗选择有限,治疗途径仍然是一个挑战。蛋白质组学平台已被用于发现多种疾病的生物标志物,这一工具可能有助于PD患者疾病进展的诊断和监测。因此,本系统综述重点分析通过蛋白质组学平台鉴定的基于血液的帕金森病候选生物标志物(CB)。本研究系统地检索了2010年至2020年间发表在六个数据库(EMBASE、Cochrane、Ovid Medline、Scopus、Science Direct和PubMed)中的文章。在检索到的504篇文章中,选择了12项对照帕金森病研究进行进一步分析。在选定的12项对照研究中,共鉴定出115种候选生物标志物(CB),其中23种CB在两个以上队列中具有可重复性。使用PANTHER Go-Slim分类系统和STRING网络,分析了生物标志物之间的基因功能和蛋白质相互作用。我们的分析突出了载脂蛋白A-I(ApoA-I),它在脂质代谢、氧化应激和神经保护中至关重要,在五个队列中具有高度可重复性,在四个队列中一致下调。由于ApoA-I在不同血液成分、蛋白质组学平台和各大洲都具有高度可重复性,本文讨论了其作为帕金森病生物标志物与胆固醇、他汀类药物和氧化应激的关系,以及它在帕金森病发病机制中的作用。本研究通过对帕金森病的蛋白质组学分析,将ApoA-I鉴定为一种潜在的生物标志物,用于疾病进展的早期诊断和预测。

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