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标题：Urine proteomics analysis of patients with neuronal ceroid lipofuscinoses
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作者：Katharina Iwan ; Robert Clayton ; Philippa Mills 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：2
页码：1-33
DOI：10.1016/j.isci.2020.102020
语种：English
出版社：Elsevier
摘要：SummaryThe 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.Graphical AbstractDisplay OmittedHighlights•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 humansDisease; Systems Biology; Proteomics