Neurofilaments in motor neuron disorders: towards promising diagnostic and prognostic biomarkers.
Neurofilaments in motor neuron disorders: towards promising diagnostic and prognostic biomarkers.
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DOI：
10.1186/s13024-020-00406-3
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发表时间：
2020-10-15
影响因子：
15.1
通讯作者：
Mandrioli J
中科院分区：
文献类型：
--
作者：
Zucchi E;Bonetto V;Sorarù G;Martinelli I;Parchi P;Liguori R;Mandrioli J
运动神经元疾病（MND）是病因学和生物学上异质性的疾病。运动神经元变性的病理生物学在很大程度上仍然是未知的，并且没有有效的治疗方法。异质性和缺乏特异性疾病生物标志物已被指定为过去临床试验失败的主要原因，生物标志物的发现是当今MND研究议程的关键。在过去的十年中，神经丝（NFs）已成为有前途的生物标志物的神经退行性疾病的临床评估。神经纤维是一种支架蛋白，其主要结构功能是促进有髓鞘轴突的轴突细胞骨架。神经纤维在脑脊液和外周血中的释放是轴突变性的结果，与主要的因果事件无关。由于目前高灵敏度的自动化技术能够在飞摩尔范围内精确定量生物流体中的蛋白质，现在不仅可以可靠地测量CSF中的NF，还可以可靠地测量血液中的NF。在这篇综述中，我们将讨论NF如何影响ALS和其他MND的研究和临床管理。除了通过区分具有不同临床演变和严重程度的MND而有助于早期诊断之外，NF还可以为临床试验中早期招募患者提供有用的工具。由于其在疾病中的稳定性，NF传达了预后信息，并且在更大的范围内，有助于将患者分层为同质组。我们也将根据现有的文献讨论生物液体中NF评估的缺点，以预测生物标志物在MND临床中的最适当使用。
Motor neuron diseases (MNDs) are etiologically and biologically heterogeneous diseases. The pathobiology of motor neuron degeneration is still largely unknown, and no effective therapy is available. Heterogeneity and lack of specific disease biomarkers have been appointed as leading reasons for past clinical trial failure, and biomarker discovery is pivotal in today’s MND research agenda. In the last decade, neurofilaments (NFs) have emerged as promising biomarkers for the clinical assessment of neurodegeneration. NFs are scaffolding proteins with predominant structural functions contributing to the axonal cytoskeleton of myelinated axons. NFs are released in CSF and peripheral blood as a consequence of axonal degeneration, irrespective of the primary causal event. Due to the current availability of highly-sensitive automated technologies capable of precisely quantify proteins in biofluids in the femtomolar range, it is now possible to reliably measure NFs not only in CSF but also in blood. In this review, we will discuss how NFs are impacting research and clinical management in ALS and other MNDs. Besides contributing to the diagnosis at early stages by differentiating between MNDs with different clinical evolution and severity, NFs may provide a useful tool for the early enrolment of patients in clinical trials. Due to their stability across the disease, NFs convey prognostic information and, on a larger scale, help to stratify patients in homogenous groups. Shortcomings of NFs assessment in biofluids will also be discussed according to the available literature in the attempt to predict the most appropriate use of the biomarker in the MND clinic.
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影响因子：
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作者：
Boylan, Kevin B.;Glass, Jonathan D.;Shaw, Gerry
通讯作者：
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作者：
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影响因子：
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作者：
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DOI：
10.1080/21678421.2019.1646769
发表时间：
2019-08-20
影响因子：
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作者：
Benatar, Michael;Wuu, Joanne;Malaspina, Andrea
通讯作者：
Malaspina, Andrea