Knockout of reactive astrocyte activating factors slows disease progression in an ALS mouse model
Kevin A. Guttenplan, Maya K. Weigel, Drew Adler, Julien Couthouis, Shane A. Liddelow, Aaron D. Gitler, Ben A. Barres
Abstract
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 G93A ALS mouse model, providing evidence for gliosis as a potential ALS therapeutic target.
Topics & Concepts
GliosisMicrogliaAstrocyteSOD1PathogenesisNeuroscienceKnockout mouseAmyotrophic lateral sclerosisMechanism (biology)BiologyDiseaseNeuroinflammationInflammationImmunologyMedicineCentral nervous systemPathologyGeneGeneticsPhilosophyEpistemologyAmyotrophic Lateral Sclerosis ResearchNeuroinflammation and Neurodegeneration MechanismsIntracerebral and Subarachnoid Hemorrhage Research