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Here we use Alexander disease, a serious degenerative neurological disorder caused by astrocyte dysfunction, to identify glial-derived NO as a signalling molecule triggering astrocyte-mediated neuronal degeneration. We further find that NO acts through cGMP signalling in neurons to promote cell death. Glial cells themselves also degenerate, via the DNA damage response and p53. Our findings thus define a specific mechanism for glial-induced non-cell autonomous neuronal cell death, and identify a potential therapeutic target for reducing cellular toxicity in Alexander disease, and possibly other neurodegenerative disorders with glial dysfunction.<\/jats:p>","DOI":"10.1038\/ncomms9966","type":"journal-article","created":{"date-parts":[[2015,11,26]],"date-time":"2015-11-26T12:25:26Z","timestamp":1448540726000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Nitric oxide mediates glial-induced neurodegeneration in Alexander disease"],"prefix":"10.1038","volume":"6","author":[{"given":"Liqun","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy L.","family":"Hagemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Kalwa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Michel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albee","family":"Messing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mel B.","family":"Feany","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,11,26]]},"reference":[{"key":"BFncomms9966_CR1","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1016\/j.neuron.2008.10.013","volume":"60","author":"BA Barres","year":"2008","unstructured":"Barres, B. 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