PMC:6610326 / 56987-58764
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/6610326","sourcedb":"PMC","sourceid":"6610326","source_url":"https://www.ncbi.nlm.nih.gov/pmc/6610326","text":"There is increasing evidence that astrocytes mediate MN degeneration via the release of neurotoxic factors. Soluble toxic compounds produced by astrocytes expressing mutant SOD1 trigger the selective loss of spinal MNs (Nagai et al., 2007), but not spinal GABAergic neurons, consistent with the specific vulnerability of these cells in ALS (Nagai et al., 2007). Astrocytes in the ventral spinal cord can be distinguished from astrocytes in the dorsal spinal cord by expression of semaphorin A3 (Sema3a), which is implicated in the specific vulnerability to FF-MNs in ALS (see section “Neuroprotective and Neurotoxic Factor Expression in MN Subpopulations” below). Furthermore, astrocytes are also implicated in MN loss and disease progression by mediating AMPA receptor-induced excitotoxicity via EAAT2/GLT-1, as discussed below (section “Neuronal Excitability”). Expression of mutant TDP-43M337V in rat astrocytes led to down-regulation of neurotrophic genes, up-regulation of neurotoxic genes and progressive MN degeneration (Tong et al., 2013; Huang et al., 2014). Conditioned medium from primary astrocyte cultures of SOD1G86R and TDP-43A315T mice also induces MN death through activation of sodium channels and nitro-oxidative stress (Rojas et al., 2014). Furthermore, astrocytes expressing mutant FUSR521G trigger MN death by secreting pro-inflammatory tumor necrosis factor (TNF)-α (Kia et al., 2018). SOD1G93A aggregates in astrocytes appear in late disease stages, selectively in regions with extensive neuronal degeneration and prominent astrogliosis (Jaarsma et al., 2008). This raises the possibility that astroglial aggregate formation is triggered by MN degeneration, implying that disease may spread from neurons to glia (Jaarsma et al., 2008; Sun et al., 2015).","tracks":[{"project":"2_test","denotations":[{"id":"31316328-17435755-38515664","span":{"begin":234,"end":238},"obj":"17435755"},{"id":"31316328-17435755-38515665","span":{"begin":355,"end":359},"obj":"17435755"},{"id":"31316328-23714777-38515666","span":{"begin":1041,"end":1045},"obj":"23714777"},{"id":"31316328-24447103-38515667","span":{"begin":1061,"end":1065},"obj":"24447103"},{"id":"31316328-24570655-38515668","span":{"begin":1254,"end":1258},"obj":"24570655"},{"id":"31316328-29380416-38515669","span":{"begin":1402,"end":1406},"obj":"29380416"},{"id":"31316328-18305242-38515670","span":{"begin":1578,"end":1582},"obj":"18305242"},{"id":"31316328-18305242-38515671","span":{"begin":1753,"end":1757},"obj":"18305242"},{"id":"31316328-26621731-38515672","span":{"begin":1771,"end":1775},"obj":"26621731"}],"attributes":[{"subj":"31316328-17435755-38515664","pred":"source","obj":"2_test"},{"subj":"31316328-17435755-38515665","pred":"source","obj":"2_test"},{"subj":"31316328-23714777-38515666","pred":"source","obj":"2_test"},{"subj":"31316328-24447103-38515667","pred":"source","obj":"2_test"},{"subj":"31316328-24570655-38515668","pred":"source","obj":"2_test"},{"subj":"31316328-29380416-38515669","pred":"source","obj":"2_test"},{"subj":"31316328-18305242-38515670","pred":"source","obj":"2_test"},{"subj":"31316328-18305242-38515671","pred":"source","obj":"2_test"},{"subj":"31316328-26621731-38515672","pred":"source","obj":"2_test"}]},{"project":"0_colil","denotations":[{"id":"31316328-17435755-631121","span":{"begin":234,"end":238},"obj":"17435755"},{"id":"31316328-17435755-631122","span":{"begin":355,"end":359},"obj":"17435755"},{"id":"31316328-23714777-631123","span":{"begin":1041,"end":1045},"obj":"23714777"},{"id":"31316328-24447103-631124","span":{"begin":1061,"end":1065},"obj":"24447103"},{"id":"31316328-24570655-631125","span":{"begin":1254,"end":1258},"obj":"24570655"},{"id":"31316328-29380416-631126","span":{"begin":1402,"end":1406},"obj":"29380416"},{"id":"31316328-18305242-631127","span":{"begin":1578,"end":1582},"obj":"18305242"},{"id":"31316328-18305242-631128","span":{"begin":1753,"end":1757},"obj":"18305242"},{"id":"31316328-26621731-631129","span":{"begin":1771,"end":1775},"obj":"26621731"}],"attributes":[{"subj":"31316328-17435755-631121","pred":"source","obj":"0_colil"},{"subj":"31316328-17435755-631122","pred":"source","obj":"0_colil"},{"subj":"31316328-23714777-631123","pred":"source","obj":"0_colil"},{"subj":"31316328-24447103-631124","pred":"source","obj":"0_colil"},{"subj":"31316328-24570655-631125","pred":"source","obj":"0_colil"},{"subj":"31316328-29380416-631126","pred":"source","obj":"0_colil"},{"subj":"31316328-18305242-631127","pred":"source","obj":"0_colil"},{"subj":"31316328-18305242-631128","pred":"source","obj":"0_colil"},{"subj":"31316328-26621731-631129","pred":"source","obj":"0_colil"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#ec9398","default":true},{"id":"0_colil","color":"#93b2ec"}]}]}}