Microglia induce motor neuron death via the classical NF-κB pathway in amyotrophic lateral sclerosis

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Date

2014-02

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Cell Press, Neuron

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Abstract

Neuroinflammation is one of the most striking hallmarks of amyotrophic lateral sclerosis (ALS). Nuclear Factor-kappa B (NF-κB), a master regulator of inflammation, is upregulated in spinal cords of ALS patients and SOD1-G93A mice. In this study, we show that selective NF-κB inhibition in ALS astrocytes is not sufficient to rescue motor neuron (MN) death. However, the localization of NF-κB activity and subsequent deletion of NF-κB signaling in microglia led to rescued MNs from microglial-mediated death in vitro and extended survival in ALS mice by impairing pro-inflammatory microglial activation. Conversely, constitutive activation of NF-κB selectively in WT microglia induced gliosis and MN death in vitro and in vivo. Taken together, these data provide a mechanism by which microglia induce MN death in ALS, and suggest a novel therapeutic target that can be modulated to slow the progression of ALS and possibly other neurodegenerative diseases by which microglial activation plays a role.

Description

Professional Biological Sciences: 1st Place (The Ohio State University Edward F. Hayes Graduate Research Forum)

Keywords

ALS, microglia, neuroinflammation, neurodegeneration, motor neurons

Citation

http://dx.doi.org/10.1016/j.neuron.2014.01.013