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Opportunities and challenges of alpha-synuclein as a potential biomarker for Parkinson’s disease and other synucleinopathies
npj Parkinson's Disease ( IF 9.304 ) Pub Date : 2022-07-22 , DOI: 10.1038/s41531-022-00357-0
Pedro Magalhães 1 , Hilal A Lashuel 1
Affiliation  

Parkinson’s disease (PD), the second most common progressive neurodegenerative disease, develops and progresses for 10–15 years before the clinical diagnostic symptoms of the disease are manifested. Furthermore, several aspects of PD pathology overlap with other neurodegenerative diseases (NDDs) linked to alpha-synuclein (aSyn) aggregation, also called synucleinopathies. Therefore, there is an urgent need to discover and validate early diagnostic and prognostic markers that reflect disease pathophysiology, progression, severity, and potential differences in disease mechanisms between PD and other NDDs. The close association between aSyn and the development of pathology in synucleinopathies, along with the identification of aSyn species in biological fluids, has led to increasing interest in aSyn species as potential biomarkers for early diagnosis of PD and differentiate it from other synucleinopathies. In this review, we (1) provide an overview of the progress toward mapping the distribution of aSyn species in the brain, peripheral tissues, and biological fluids; (2) present comparative and critical analysis of previous studies that measured total aSyn as well as other species such as modified and aggregated forms of aSyn in different biological fluids; and (3) highlight conceptual and technical gaps and challenges that could hinder the development and validation of reliable aSyn biomarkers; and (4) outline a series of recommendations to address these challenges. Finally, we propose a combined biomarker approach based on integrating biochemical, aggregation and structure features of aSyn, in addition to other biomarkers of neurodegeneration. We believe that capturing the diversity of aSyn species is essential to develop robust assays and diagnostics for early detection, patient stratification, monitoring of disease progression, and differentiation between synucleinopathies. This could transform clinical trial design and implementation, accelerate the development of new therapies, and improve clinical decisions and treatment strategies.



中文翻译:

α-突触核蛋白作为帕金森病和其他突触核蛋白病的潜在生物标志物的机遇和挑战

帕金森病 (PD) 是第二种最常见的进行性神经退行性疾病,在疾病的临床诊断症状出现之前会发展和发展 10-15 年。此外,PD 病理学的几个方面与其他与 α-突触核蛋白 (aSyn) 聚集相关的神经退行性疾病 (NDD) 重叠,也称为突触核蛋白病。因此,迫切需要发现和验证反映疾病病理生理学、进展、严重程度以及 PD 与其他 NDD 之间疾病机制的潜在差异的早期诊断和预后标志物。aSyn 与突触核蛋白病病理发展之间的密切关联,以及生物体液中 aSyn 种类的鉴定,导致人们越来越关注将 aSyn 物种作为早期诊断 PD 并将其与其他突触核蛋白病区分开来的潜在生物标志物。在这篇综述中,我们 (1) 概述了绘制大脑、外周组织和生物体液中 aSyn 物种分布的进展;(2) 对先前测量总 aSyn 以及其他物种(例如不同生物流体中 aSyn 的修饰和聚集形式)的研究进行比较和批判性分析;(3) 强调可能阻碍可靠 aSyn 生物标志物开发和验证的概念和技术差距和挑战;(4) 概述应对这些挑战的一系列建议。最后,我们提出了一种基于整合 aSyn 的生化、聚集和结构特征的组合生物标志物方法,除了神经退行性变的其他生物标志物。我们相信,捕获 aSyn 物种的多样性对于开发用于早期检测、患者分层、疾病进展监测和突触核蛋白病之间区分的强大分析和诊断至关重要。这可以改变临床试验的设计和实施,加速新疗法的开发,并改进临床决策和治疗策略。

更新日期:2022-07-22
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