Knockout of reactive astrocyte activating factors slows disease progression in an ALS mouse model.

Guttenplan, Kevin A; Weigel, Maya K; Adler, Drew I; Couthouis, Julien; Liddelow, Shane A; Gitler, Aaron D; Barres, Ben A · Nat Commun · 2020

basic_science · Level V

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Abstract

Reactive astrocytes have been implicated in the pathogenesis of neurodegenerative diseases, including a non-cell autonomous effect on motor neuron survival in ALS. We previously defined a mechanism by which microglia release three factors, IL-1α, TNFα, and C1q, to induce neurotoxic astrocytes. Here we report that knocking out these three factors markedly extends survival in the SOD1<sup>G93A</sup> ALS mouse model, providing evidence for gliosis as a potential ALS therapeutic target.

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