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新方法快速区分帕金森病和多系统萎缩症
2020-02-12 13:37

美国德克萨斯大学麦戈文医学院Claudio Soto小组的研究利用α-突触核蛋白的特异性区分了帕金森病和多系统萎缩症。2020年2月5日,《自然》在线发表了这项成果。

研究人员发现,α-突触核蛋白-PMCA分析技术可以用来区分帕金森氏病患者和多系统萎缩患者的脑脊液样本,总灵敏度为95.4%。研究人员结合生化、生物物理和生物学方法对α-突触核蛋白-PMCA的产物进行了分析,发现脑脊液中α-突触核蛋白聚集体的特征可以轻松地区分帕金森氏病和多系统萎缩症。研究人员还发现,从脑脊液中扩增聚集体的性质与从大脑中扩增聚集体的性质相似。这些发现表明,帕金森氏病和多系统萎缩相关的α-突触核蛋白聚集体对应于α-突触核蛋白的不同构象,可以通过α-突触核蛋白-PMCA进行扩增和检测。这些结果可能有助于增进人们对α-突触核蛋白错折叠机制和涉及不同突触核仁病聚集体结构的了解,也可能使的生物化学分析方法得以发展,以更好的区分帕金森氏病和多系统萎缩。

据了解,突触核蛋白病是与α-突触核蛋白的错误折叠和聚集有关的神经退行性疾病,包括帕金森氏病、路易体痴呆和多系统萎缩症。临床上,区分帕金森氏病和多系统萎缩症具有挑战性,特别是在疾病的早期阶段。已经提出了在不同突触核变病中聚集的α-突触核蛋白代表不同构象的α-突触核蛋白类型,它们可以自我传播并从细胞扩散到细胞。蛋白质错误折叠循环扩增(PMCA)是一种先前已被用来检测脑脊液样品中α-突触核蛋白聚集体的技术,其具有高灵敏度性和特异性。

附:英文原文

Title: Discriminating α-synuclein strains in Parkinson’s disease and multiple system atrophy

Author: Mohammad Shahnawaz, Abhisek Mukherjee, Sandra Pritzkow, Nicolas Mendez, Prakruti Rabadia, Xiangan Liu, Bo Hu, Ann Schmeichel, Wolfgang Singer, Gang Wu, Ah-Lim Tsai, Hamid Shirani, K. Peter R. Nilsson, Phillip A. Low, Claudio Soto

Issue&Volume: 2020-02-05

Abstract: Synucleinopathies are neurodegenerative diseases that are associated with the misfolding and aggregation of α-synuclein, including Parkinson’s disease, dementia with Lewy bodies and multiple system atrophy1. Clinically, it is challenging to differentiate Parkinson’s disease and multiple system atrophy, especially at the early stages of disease2. Aggregates of α-synuclein in distinct synucleinopathies have been proposed to represent different conformational strains of α-synuclein that can self-propagate and spread from cell to cell3,4,5,6. Protein misfolding cyclic amplification (PMCA) is a technique that has previously been used to detect α-synuclein aggregates in samples of cerebrospinal fluid with high sensitivity and specificity7,8. Here we show that the α-synuclein-PMCA assay can discriminate between samples of cerebrospinal fluid from patients diagnosed with Parkinson’s disease and samples from patients with multiple system atrophy, with an overall sensitivity of 95.4%. We used a combination of biochemical, biophysical and biological methods to analyse the product of α-synuclein-PMCA, and found that the characteristics of the α-synuclein aggregates in the cerebrospinal fluid could be used to readily distinguish between Parkinson’s disease and multiple system atrophy. We also found that the properties of aggregates that were amplified from the cerebrospinal fluid were similar to those of aggregates that were amplified from the brain. These findings suggest that α-synuclein aggregates that are associated with Parkinson’s disease and multiple system atrophy correspond to different conformational strains of α-synuclein, which can be amplified and detected by α-synuclein-PMCA. Our results may help to improve our understanding of the mechanism of α-synuclein misfolding and the structures of the aggregates that are implicated in different synucleinopathies, and may also enable the development of a biochemical assay to discriminate between Parkinson’s disease and multiple system atrophy.

DOI: 10.1038/s41586-020-1984-7

Source: https://www.nature.com/articles/s41586-020-1984-7

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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