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

  • Chang Liu , Kun Hong , Huifang Chen , Yanping Niu , Weisong Duan , Yakun Liu , Yingxiao Ji , Binbin Deng , Yuanyuan Li , Zhongyao Li , Di Wen und Chunyan Li EMAIL logo
Veröffentlicht/Copyright: 22. März 2019
Biological Chemistry
Aus der Zeitschrift Biological Chemistry Band 400 Heft 5

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.

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

Acknowledgments

This study was supported by grants from the Natural Science Foundation of China (C090301-30870882); and Hebei Science and Technology Department (0647007D).

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2018-0204).

Received: 2018-04-02
Accepted: 2018-10-06
Published Online: 2019-03-22
Published in Print: 2019-05-27

©2019 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/hsz-2018-0204
Schlagwörter für diesen Artikel
amyotrophic lateral sclerosis (ALS); autophagy; CX3CR1; inflammatory

Artikel in diesem Heft

  1. Frontmatter
  2. Reviews
  3. Complexity of type IV collagens: from network assembly to function
  4. Structural and mechanistic aspects of S-S bonds in the thioredoxin-like family of proteins
  5. Oxidative stress and antioxidants in the pathophysiology of malignant melanoma
  6. Research Articles/Short Communications
  7. Genes and Nucleic Acids
  8. Dynamic characteristics of the mitochondrial genome in SCNT pigs
  9. Protein Structure and Function
  10. Conversion of chenodeoxycholic acid to cholic acid by human CYP8B1
  11. Molecular Medicine
  12. The comparative biochemistry of viruses and humans: an evolutionary path towards autoimmunity
  13. MiR-23a-3p-regulated abnormal acetylation of FOXP3 induces regulatory T cell function defect in Graves’ disease
  14. Cell Biology and Signaling
  15. Evidence for a protective role of the CX3CL1/CX3CR1 axis in a model of amyotrophic lateral sclerosis
  16. LncRNA TINCR/microRNA-107/CD36 regulates cell proliferation and apoptosis in colorectal cancer via PPAR signaling pathway based on bioinformatics analysis
  17. Regulatory effect of hsa-miR-5590-3P on TGFβ signaling through targeting of TGFβ-R1, TGFβ-R2, SMAD3 and SMAD4 transcripts
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