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Proteomic analysis of exosome-enriched fractions derived from cerebrospinal fluid of amyotrophic lateral sclerosis patients.

Authors
  • Hayashi, Noriko1
  • Doi, Hiroshi2
  • Kurata, Yoichi3
  • Kagawa, Hiroyuki3
  • Atobe, Yoshitoshi4
  • Funakoshi, Kengo4
  • Tada, Mikiko1
  • Katsumoto, Atsuko1
  • Tanaka, Kenichi1
  • Kunii, Misako1
  • Nakamura, Haruko1
  • Takahashi, Keita1
  • Takeuchi, Hideyuki1
  • Koyano, Shigeru1
  • Kimura, Yayoi3
  • Hirano, Hisashi3
  • Tanaka, Fumiaki5
  • 1 Department of Neurology and Stroke Medicine, Yokohama, Japan. , (Japan)
  • 2 Department of Neurology and Stroke Medicine, Yokohama, Japan. Electronic address: [email protected] , (Japan)
  • 3 Advanced Medical Research Center, Yokohama, Japan. , (Japan)
  • 4 Department of Neuroanatomy, Yokohama City University Graduate School of Medicine, Yokohama, Japan. , (Japan)
  • 5 Department of Neurology and Stroke Medicine, Yokohama, Japan. Electronic address: [email protected] , (Japan)
Type
Published Article
Journal
Neuroscience research
Publication Date
Nov 01, 2020
Volume
160
Pages
43–49
Identifiers
DOI: 10.1016/j.neures.2019.10.010
PMID: 31669371
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. Copyright © 2019 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.

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