Abstract
Dominant mutations in superoxide dismutase cause amyotrophic lateral sclerosis (ALS), an adult-onset neurodegenerative disease that is characterized by the loss of motor neurons. Using mice carrying a deletable mutant gene, diminished mutant expression in astrocytes did not affect onset, but delayed microglial activation and sharply slowed later disease progression. These findings demonstrate that mutant astrocytes are viable targets for therapies for slowing the progression of non-cell autonomous killing of motor neurons in ALS.
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 / enzymology*
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Amyotrophic Lateral Sclerosis / genetics
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Amyotrophic Lateral Sclerosis / physiopathology
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Animals
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Astrocytes / enzymology*
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Cell Death / genetics
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Disease Models, Animal
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Disease Progression
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Genes, Dominant
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Genetic Therapy / methods
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Glial Fibrillary Acidic Protein / genetics
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Glial Fibrillary Acidic Protein / metabolism
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Gliosis / enzymology*
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Gliosis / genetics
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Gliosis / physiopathology
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Humans
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Integrases / genetics
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Mice
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Mice, Transgenic
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Microglia / enzymology
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Mutation / genetics
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Nerve Degeneration / enzymology*
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Nerve Degeneration / genetics
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Nerve Degeneration / physiopathology
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Nitric Oxide / metabolism
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Nitric Oxide Synthase Type II / metabolism
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Oxidative Stress / genetics
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Spinal Cord / enzymology
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Spinal Cord / pathology
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Spinal Cord / physiopathology
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Superoxide Dismutase / genetics*
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Superoxide Dismutase-1
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Survival Rate
Substances
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Glial Fibrillary Acidic Protein
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SOD1 protein, human
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Nitric Oxide
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Nitric Oxide Synthase Type II
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Sod1 protein, mouse
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Superoxide Dismutase
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Superoxide Dismutase-1
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Cre recombinase
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Integrases