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{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/6610326","sourcedb":"PMC","sourceid":"6610326","source_url":"https://www.ncbi.nlm.nih.gov/pmc/6610326","text":"Differential expression of pro-survival or toxic factors is also implicated in the specific vulnerability of MN subtypes. The IGFs are proteins with high homology to insulin that form part of the IGF “axis” that promotes cell proliferation and inhibits apoptosis. In the normal rat, IGF-I is highly expressed in oculomotor neurons, where it is protective against glutamate-induced toxicity (Hedlund et al., 2010; Allodi et al., 2016). This may be due to activation of the PI3K/Akt and p44/42 MAPK pathways, which both inhibit apoptosis (Siddle et al., 2001; Sakowski et al., 2009). In addition, its associated receptor, IGF-I receptor (IGF-IR), is also highly expressed in oculomotor neurons and on the extraocular muscle endplate (Allodi et al., 2016). IGF-IR is important for the survival of neurons following hypoxic/ischemic injury (Vincent and Feldman, 2002; Liu et al., 2011) by upregulation of neuronal cellular inhibitor of apoptosis-1 (cIAP-1) and X-linked inhibitor of apoptosis (XIAP) (Liu et al., 2011). Delivery of IGF-II using AAV9 to the muscle of mutant SOD1G93A mice extended life-span by 10%, prevented the loss of MNs and induced motor axon regeneration (Allodi et al., 2016). These findings indicate that differential expression of IGF-II and IGF-IR in oculomotor neurons might contribute to their relative resistance to degeneration in ALS/FTD.","tracks":[{"project":"2_test","denotations":[{"id":"31316328-20826431-38515726","span":{"begin":407,"end":411},"obj":"20826431"},{"id":"31316328-27180807-38515727","span":{"begin":428,"end":432},"obj":"27180807"},{"id":"31316328-11498020-38515728","span":{"begin":552,"end":556},"obj":"11498020"},{"id":"31316328-18608100-38515729","span":{"begin":575,"end":579},"obj":"18608100"},{"id":"31316328-27180807-38515730","span":{"begin":747,"end":751},"obj":"27180807"},{"id":"31316328-12175651-38515731","span":{"begin":858,"end":862},"obj":"12175651"},{"id":"31316328-21718528-38515732","span":{"begin":876,"end":880},"obj":"21718528"},{"id":"31316328-21718528-38515733","span":{"begin":1009,"end":1013},"obj":"21718528"},{"id":"31316328-27180807-38515734","span":{"begin":1189,"end":1193},"obj":"27180807"}],"attributes":[{"subj":"31316328-20826431-38515726","pred":"source","obj":"2_test"},{"subj":"31316328-27180807-38515727","pred":"source","obj":"2_test"},{"subj":"31316328-11498020-38515728","pred":"source","obj":"2_test"},{"subj":"31316328-18608100-38515729","pred":"source","obj":"2_test"},{"subj":"31316328-27180807-38515730","pred":"source","obj":"2_test"},{"subj":"31316328-12175651-38515731","pred":"source","obj":"2_test"},{"subj":"31316328-21718528-38515732","pred":"source","obj":"2_test"},{"subj":"31316328-21718528-38515733","pred":"source","obj":"2_test"},{"subj":"31316328-27180807-38515734","pred":"source","obj":"2_test"}]},{"project":"0_colil","denotations":[{"id":"31316328-20826431-631183","span":{"begin":407,"end":411},"obj":"20826431"},{"id":"31316328-27180807-631184","span":{"begin":428,"end":432},"obj":"27180807"},{"id":"31316328-11498020-631185","span":{"begin":552,"end":556},"obj":"11498020"},{"id":"31316328-18608100-631186","span":{"begin":575,"end":579},"obj":"18608100"},{"id":"31316328-27180807-631187","span":{"begin":747,"end":751},"obj":"27180807"},{"id":"31316328-12175651-631188","span":{"begin":858,"end":862},"obj":"12175651"},{"id":"31316328-21718528-631189","span":{"begin":876,"end":880},"obj":"21718528"},{"id":"31316328-21718528-631190","span":{"begin":1009,"end":1013},"obj":"21718528"},{"id":"31316328-27180807-631191","span":{"begin":1189,"end":1193},"obj":"27180807"}],"attributes":[{"subj":"31316328-20826431-631183","pred":"source","obj":"0_colil"},{"subj":"31316328-27180807-631184","pred":"source","obj":"0_colil"},{"subj":"31316328-11498020-631185","pred":"source","obj":"0_colil"},{"subj":"31316328-18608100-631186","pred":"source","obj":"0_colil"},{"subj":"31316328-27180807-631187","pred":"source","obj":"0_colil"},{"subj":"31316328-12175651-631188","pred":"source","obj":"0_colil"},{"subj":"31316328-21718528-631189","pred":"source","obj":"0_colil"},{"subj":"31316328-21718528-631190","pred":"source","obj":"0_colil"},{"subj":"31316328-27180807-631191","pred":"source","obj":"0_colil"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#93abec","default":true},{"id":"0_colil","color":"#c5ec93"}]}]}}