title: Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis.
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.
authors.affiliation: Ludwig Institute for Cancer Research and Department of Medicine and Neuroscience, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093-0670, USA.
authors.forename: Koji
authors.initials: K
authors.lastname: Yamanaka
authors.forename: Seung Joo
authors.initials: SJ
authors.lastname: Chun
authors.forename: Severine
authors.initials: S
authors.lastname: Boillee
authors.forename: Noriko
authors.initials: N
authors.lastname: Fujimori-Tonou
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yamashita
authors.forename: David H
authors.initials: DH
authors.lastname: Gutmann
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takahashi
authors.forename: Hidemi
authors.initials: H
authors.lastname: Misawa
authors.forename: Don W
authors.initials: DW
authors.lastname: Cleveland
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D000818:Animals; D001253:Astrocytes / Q000201:enzymology*; D016923:Cell Death / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D005799:Genes, Dominant; D015316:Genetic Therapy / Q000379:methods; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D005911:Gliosis / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D019426:Integrases / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000201:enzymology; D009154:Mutation / Q000235:genetics; D009410:Nerve Degeneration / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics; D013116:Spinal Cord / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D015996:Survival Rate
chemical_list: D005904:Glial Fibrillary Acidic Protein; C000606290:SOD1 protein, human; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; C045073:Cre recombinase; D019426:Integrases