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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred


IMPACT FACTOR 2018: 3.014
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Volume 400, Issue 5

Issues

Evidence for a protective role of the CX3CL1/CX3CR1 axis in a model of amyotrophic lateral sclerosis

Chang Liu
  • Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, People’s Republic of China
  • Department of Rehabilitation Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, People’s Republic of China
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/ Kun Hong
  • Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, People’s Republic of China
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/ Huifang Chen
  • Department of Neurology, Hebei Province People’s Hospital, Shijiazhuang 050000, Hebei, People’s Republic of China
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/ Yanping Niu
  • Department of Rehabilitation Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, People’s Republic of China
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/ Weisong Duan
  • Neurological Laboratory of Hebei Province, Shijiazhuang 050000, Hebei, People’s Republic of China
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/ Yakun Liu
  • Neurological Laboratory of Hebei Province, Shijiazhuang 050000, Hebei, People’s Republic of China
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/ Yingxiao Ji
  • Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, People’s Republic of China
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/ Binbin Deng
  • Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, People’s Republic of China
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/ Yuanyuan Li
  • Neurological Laboratory of Hebei Province, Shijiazhuang 050000, Hebei, People’s Republic of China
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/ Zhongyao Li
  • Neurological Laboratory of Hebei Province, Shijiazhuang 050000, Hebei, People’s Republic of China
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/ Di Wen
  • Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, People’s Republic of China
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/ Chunyan Li
  • Corresponding author
  • Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, People’s Republic of China
  • Neurological Laboratory of Hebei Province, Shijiazhuang 050000, Hebei, People’s Republic of China
  • Institute of Cardiocerebrovascular Disease, West Heping Road 215, Shijiazhuang 050000, Hebei, People’s Republic of China
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Published Online: 2019-03-22 | DOI: https://doi.org/10.1515/hsz-2018-0204

Abstract

Aberrant microglial activation and neuroinflammation is a pathological hallmark of amyotrophic lateral sclerosis (ALS). Fractalkine (CX3CL1) is mostly expressed on neuronal cells. The fractalkine receptor (CX3CR1) is predominantly expressed on microglia. Many progressive neuroinflammatory disorders show disruption of the CX3CL1/CX3CR1 communication system. But the exact role of the CX3CL1/CX3CR1 in ALS pathology remains unknown. F1 nontransgenic/CX3CR1+/− females were bred with SOD1G93A/CX3CR1+/− males to produce F2 SOD1G93A/CX3CR1−/−, SOD1G93A/CX3CR1+/+. We analyzed end-stage (ES) SOD1G93A/CX3CR1−/− mice and progression-matched SOD1G93A/CX3CR1+/+ mice. Our study showed that the male SOD1G93A/CX3CR1−/− mice died sooner than male SOD1G93A/CX3CR1+/+ mice. In SOD1G93A/CX3CR1−/− mice demonstrated more neuronal cell loss, more microglial activation and exacerbated SOD1 aggregation at the end-stage of ALS. The NF-κB pathway was activated; the autophagy-lysosome degradation pathway and the autophagosome maturation were impaired. Our results indicated that the absence of CX3CR1/CX3CL1 signaling in the central nervous system (CNS) may worsen neurodegeneration. The CX3CL1/CX3CR1 communication system has anti-inflammatory and neuroprotective effects and plays an important role in maintaining autophagy activity. This effort may lead to new therapeutic strategies for neuroprotection and provide a therapeutic target for ALS patients.

This article offers supplementary material which is provided at the end of the article.

Keywords: amyotrophic lateral sclerosis (ALS); autophagy; CX3CR1; inflammatory

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About the article

aChang Liu and Kun Hong: These authors contributed equally to this work.


Received: 2018-04-02

Accepted: 2018-10-06

Published Online: 2019-03-22

Published in Print: 2019-05-27


Citation Information: Biological Chemistry, Volume 400, Issue 5, Pages 651–661, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2018-0204.

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