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

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.

journal_name

Biol Chem

journal_title

Biological chemistry

authors

Liu C,Hong K,Chen H,Niu Y,Duan W,Liu Y,Ji Y,Deng B,Li Y,Li Z,Wen D,Li C

doi

10.1515/hsz-2018-0204

subject

Has Abstract

pub_date

2019-04-24 00:00:00

pages

651-661

issue

5

eissn

1431-6730

issn

1437-4315

pii

/j/bchm.just-accepted/hsz-2018-0204/hsz-2018-0204.

journal_volume

400

pub_type

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