NF‐κB activation in astrocytes drives a stage‐specific beneficial neuroimmunological response in ALS

Journal: The EMBO Journal

Published: 2018-06-06

DOI: 10.15252/embj.201798697

Affiliations: 7

Authors: 22

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Research Highlight

The paradox of neuroimmune activation in ALS

© National Institutes of Health/Stocktrek Images/Getty

© National Institutes of Health/Stocktrek Images/Getty

Star-shaped support cells in the brain activate an immune response that helps protect against motor neuron loss in the early stages of amyotrophic lateral sclerosis (ALS). Yet, this same immune activation can accelerate neurodegeneration in later stages of the disease.

Findings from a mouse study, that included scientists from Roche, suggest that stage-dependent modulation of this immune process may be an effective therapeutic strategy for ALS patients.

The researchers activated a key cell-signaling pathway in the spinal cord astrocytes of a mouse model of ALS. They observed a proliferation of neuroimmune cells, called microglia, which resulted in delayed symptom onset but accelerated disease progression.

Pre-symptomatic treatment with an experimental Roche drug designed to enhance microglia function by blunting the immunosuppressive function of cannabinoid CB2 receptors led to a decrease in disease burden on a molecular level. A similar strategy could prove beneficial for those with a genetic risk for ALS who have yet to exhibit signs of the disease.

Supported content

  1. The EMBO Journal 37, e98697 (2018). doi: 10.15252/embj.201798697
Institutions FC
Roche Pharma Research and Early Development (Roche pRED), Switzerland 0.45
Department of Neurology, Ulm University, Germany 0.25
Institute of Physiological Chemistry, Ulm University, Germany 0.14
Institute of Anatomy and Cell Biology, Ulm University, Germany 0.07
Institute of Immunology, Ulm University, Germany 0.05
Natural and Medical Sciences Institute (NMI), Germany 0.02
University of Tübingen (Uni Tübingen), Germany 0.02

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