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

• Published in: Nature communications Vol. 11; no. 1; pp. 3753 - 9
• Main Authors: Guttenplan, Kevin A., Weigel, Maya K., Adler, Drew I., Couthouis, Julien, Liddelow, Shane A., Gitler, Aaron D., Barres, Ben A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.07.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/51; 631/378/1689/1285; 631/378/2596/1308; 64/60; Amyotrophic lateral sclerosis; Astrocytes; Gliosis; Humanities and Social Sciences; Microglia; multidisciplinary; Neurodegenerative diseases; Neurotoxicity; Pathogenesis; Rodents; Science; Science (multidisciplinary); Survival; Therapeutic applications; Transcription factors; Tumor necrosis factor-α
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-17514-9

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 G93A ALS mouse model, providing evidence for gliosis as a potential ALS therapeutic target. Astrocyte activation may contribute to neurodegenerative disease. Here the authors show that the combined knockout of three factors known to promote astrogliosis, IL-1α, TNFα and C1qa, leads to improved survival in the SOD1 G93A mouse model of ALS.