Astrocytes from Familial and Sporadic ALS Patients are Toxic to Motor Neurons
By Amanda M. Haidet-Phillips, Mark E. Hester, Carlos J. Miranda, K. Meyer, Lyndsey Braun, Ashley E. Frakes, SungWon Song, S. Likhite, M. Murtha, K. Foust and 7 more. Nature Biotechnology, 2011
790 citations recorded by the source corpus.
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.
Subfields: Genetics, Molecular Biology, Neurology
View Paper: https://www.semanticscholar.org/paper/01ff875cb78c928de1306cb3a19304dd551f70e7
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Citations in the corpus
- Microglia induce motor neuron death via the classical NF-κB pathway in amyotrophic lateral sclerosis (2014, positive): “We utilized an embryonic stem cell line containing an Hb9-GFP reporter, which we and others have shown recapitulate aspects of MN pathology and cell death when cocultured with ALS glia (Di Giorgio et al., 2007; Haidet-Phillips et al., 2011; Nagai et al., 2007; Wichterle et al., 2002).”
- Astrocyte reactivity and reactive astrogliosis: costs and benefits. (2014, background): “More recent data suggest that at least in some forms of ALS, the neuronal damage is mediated by oligodendrocytes (111), microglia (25, 253), and astrocytes (57, 88, 155, 268), which thus emerge as a novel therapeutic target for this devastating disease.”
- Converging mechanisms in ALS and FTD: Disrupted RNA and protein homeostasis (2013, positive): “Kaspar and colleagues (Haidet-Phillips et al., 2011) reported the very surprising finding that astrocytes derived from autopsy samples from sporadic ALS patients are also toxic to motor neurons .”