期刊
NEUROSCIENCE RESEARCH
卷 160, 期 -, 页码 43-49出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neures.2019.10.010
关键词
Exosome; Amyotrophic lateral sclerosis; Cerebrospinal fluid; Mass spectrometry
资金
- Creation and Innovation Centers for Advanced Interdisciplinary Research Areas
- Japan Society for the Promotion of Science [18K07503, 18K07504, 18K07532]
- Takeda Science Foundation
- Yokohama-City University [SK2804]
- Ministry of Education, Culture, Sports, Science and Technology, Japan
- Grants-in-Aid for Scientific Research [18K07503, 18K07532, 18K07504] Funding Source: KAKEN
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.
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