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 SOD1G93A ALS mouse model, providing evidence for gliosis as a potential ALS therapeutic target.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amyotrophic Lateral Sclerosis / metabolism*
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Amyotrophic Lateral Sclerosis / pathology*
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Animals
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Astrocytes / metabolism*
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Complement C1q / metabolism*
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Complement C3 / metabolism
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Disease Models, Animal
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Disease Progression*
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Humans
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Interleukin-1alpha / metabolism*
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Mice, Inbred C57BL
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Mice, Knockout
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Microglia
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Superoxide Dismutase-1 / metabolism
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Tumor Necrosis Factor-alpha / metabolism*
Substances
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Complement C3
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Interleukin-1alpha
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Tumor Necrosis Factor-alpha
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Complement C1q
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Superoxide Dismutase-1