title: Astrocytes from familial and sporadic ALS patients are toxic to motor neurons.
abstract: Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease, with astrocytes implicated as contributing substantially to motor neuron death in familial (F)ALS. However, the proposed role of astrocytes in the pathology of ALS derives in part from rodent models of FALS based upon dominant mutations within the superoxide dismutase 1 (SOD1) gene, which account for <2% of all ALS cases. Their role in sporadic (S)ALS, which affects >90% of ALS patients, remains to be established. Using astrocytes generated from postmortem tissue from both FALS and SALS patients, we show that astrocytes derived from both patient groups are similarly toxic to motor neurons. We also demonstrate that SOD1 is a viable target for SALS, as its knockdown significantly attenuates astrocyte-mediated toxicity toward motor neurons. Our data highlight astrocytes as a non-cell autonomous component in SALS and provide an in vitro model system to investigate common disease mechanisms and evaluate potential therapies for SALS and FALS.
authors.affiliation: The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Haidet-Phillips
authors.forename: Mark E
authors.initials: ME
authors.lastname: Hester
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Miranda
authors.forename: Kathrin
authors.initials: K
authors.lastname: Meyer
authors.forename: Lyndsey
authors.initials: L
authors.lastname: Braun
authors.forename: Ashley
authors.initials: A
authors.lastname: Frakes
authors.forename: SungWon
authors.initials: S
authors.lastname: Song
authors.forename: Shibi
authors.initials: S
authors.lastname: Likhite
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Murtha
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Foust
authors.forename: Meghan
authors.initials: M
authors.lastname: Rao
authors.forename: Amy
authors.initials: A
authors.lastname: Eagle
authors.forename: Anja
authors.initials: A
authors.lastname: Kammesheidt
authors.forename: Ashley
authors.initials: A
authors.lastname: Christensen
authors.forename: Jerry R
authors.initials: JR
authors.lastname: Mendell
authors.forename: Arthur H M
authors.initials: AH
authors.lastname: Burghes
authors.forename: Brian K
authors.initials: BK
authors.lastname: Kaspar
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D015415:Biomarkers; D002454:Cell Differentiation; D002460:Cell Line; D018920:Coculture Techniques; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D009154:Mutation; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1
chemical_list: D015415:Biomarkers; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1