Proteomic analysis of exosome-enriched fractions derived from cerebrospinal fluid of amyotrophic lateral sclerosis patients
Proteomic analysis of exosome-enriched fractions derived from cerebrospinal fluid of amyotrophic lateral sclerosis patients
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DOI：
10.1016/j.neures.2019.10.010
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发表时间：
2020-11-01
影响因子：
2.9
通讯作者：
Tanaka, Fumiaki
中科院分区：
文献类型：
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作者：
Hayashi, Noriko;Doi, Hiroshi;Tanaka, Fumiaki
外泌体含有许多与神经退行性疾病相关的蛋白质。为了鉴定与肌萎缩侧索硬化症（ALS）相关的新的候选生物标志物和蛋白质，我们使用凝胶过滤色谱法对从散发性ALS患者的脑脊液（CSF）中分离的富含外泌体的组分进行了液相色谱-串联质谱蛋白质组学分析。蛋白质组学数据显示，ALS患者中有3种蛋白质增加，11种蛋白质减少。来自ALS的CSF的富含外泌体的组分中增加最多的蛋白质是新的INHAT阻遏物（NIR），其与核仁功能密切相关。通过免疫组化分析，我们发现ALS患者运动神经元核的NIR减少。我们的研究结果表明，我们的方法的CSF外泌体的蛋白质组学分析的潜在效用，并表明，核仁应力可能通过近红外功能障碍在散发性ALS发病机制中发挥作用。(C)2019 Elsevier B. V.和日本神经科学学会。All rights reserved.
Exosomes contain many proteins associated with neurodegenerative diseases. To identify new candidate biomarkers and proteins associated with amyotrophic lateral sclerosis (ALS), we performed liquid chromatography-tandem mass spectrometry proteomic analysis of exosome-enriched fractions isolated from cerebrospinal fluid (CSF) of sporadic ALS patients using gel filtration chromatography. Proteomic data revealed that three proteins were increased and 11 proteins were decreased in ALS patients. The protein with the greatest increase in exosome-enriched fractions of CSF derived from ALS was novel INHAT repressor (NIR), which is closely associated with nucleolar function. By immunohistochemical analysis, we found that NIR was reduced in the nucleus of motor neurons in ALS patients. Our results demonstrate the potential utility of our methodology for proteomic analysis of CSF exosomes and suggest that nucleolar stress might play a role in sporadic ALS pathogenesis through the dysfunction of NIR. (C) 2019 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.