Urine proteomics analysis of patients with neuronal ceroid lipofuscinoses.
Urine proteomics analysis of patients with neuronal ceroid lipofuscinoses.
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DOI：
10.1016/j.isci.2020.102020
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发表时间：
2021-02-19
期刊：
影响因子：
5.8
通讯作者：
Heywood WE
中科院分区：
文献类型：
--
作者：
Iwan K;Clayton R;Mills P;Csanyi B;Gissen P;Mole SE;Palmer DN;Mills K;Heywood WE
神经性ceroid脂褐病（NCL）是一组13种罕见的神经退行性疾病，其特征是细胞储存体的积累。治疗选择很少，现有的测试不能监测疾病进展和治疗反应。然而，尿液生物标志物可以满足这一需求。CLN2患者尿液的蛋白质组学分析揭示了免疫反应途径的激活以及与未折叠蛋白反应相关的途径。CLN5和CLN6羊模型尿液分析显示细微变化。为了确认和研究候选生物标志物的相关性，建立了靶向LC-MS/MS蛋白质组学分析。我们将该分析应用于其他CLN2样本以及其他NCL患者（CLN1, CLN3, CLN5， CLN6和CLN7），并证明NCL样本中己糖氨基酶- a，天冬氨酸氨基转移酶-1和LAMP1升高，而甜菜碱-同型半胱氨酸s -甲基转移酶-1在CLN2患者中特异性升高。这些蛋白可用于监测未来治疗全身性NCL疾病的治疗效果。患有NCL的人和动物的尿液蛋白质组改变，己糖氨酸酶A和LAMP1在NCL患者中增加，甜菜碱-同型半胱氨酸s -甲基转移酶1在CLN2患者中升高，CLN5和CLN6羊模型中的蛋白质改变在人类中不受影响。系统生物学;蛋白质组学
The neuronal ceroid lipofuscinoses (NCL) are a group of 13 rare neurodegenerative disorders characterized by accumulation of cellular storage bodies. There are few therapeutic options, and existing tests do not monitor disease progression and treatment response. However, urine biomarkers could address this need. Proteomic analysis of CLN2 patient urine revealed activation of immune response pathways and pathways associated with the unfolded protein response. Analysis of CLN5 and CLN6 sheep model urine showed subtle changes. To confirm and investigate the relevance of candidate biomarkers a targeted LC-MS/MS proteomic assay was created. We applied this assay to additional CLN2 samples as well as other patients with NCL (CLN1, CLN3, CLN5, CLN6, and CLN7) and demonstrated that hexosaminidase-A, aspartate aminotransferase-1, and LAMP1 are increased in NCL samples and betaine-homocysteine S-methyltransferase-1 was specifically increased in patients with CLN2. These proteins could be used to monitor the effectiveness of future therapies aimed at treating systemic NCL disease. The urine proteome is altered in humans and animals with NCL Hexosaminidase A and LAMP1 are increased in patients with NCL Betaine-homocysteine S-methyltransferase 1 is elevated in CLN2 patients Proteins altered in CLN5 and CLN6 sheep models are not affected in humans Disease; Systems Biology; Proteomics
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