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Therefore, the identification of common disease mechanisms and therapeutics targeting these mechanisms could dramatically improve clinical outcomes. To this end, we developed induced motor neuron (iMN) models from\n                    <jats:italic>C9ORF72<\/jats:italic>\n                    and sporadic ALS patients to identify targets that are effective against these types of cases, which together comprise approximately 90% of patients. We find that iMNs from\n                    <jats:italic>C9ORF72<\/jats:italic>\n                    and several sporadic ALS patients share 2 common defects \u2014 impaired autophagosome formation and the aberrant accumulation of glutamate receptors. Moreover, we show that an anticoagulation-deficient form of activated protein C, 3K3A-APC, rescues these defects in both\n                    <jats:italic>C9ORF72<\/jats:italic>\n                    and sporadic ALS iMNs. As a result, 3K3A-APC treatment lowers\n                    <jats:italic>C9ORF72<\/jats:italic>\n                    dipeptide-repeat protein (DPR) levels, restores nuclear TDP-43 localization, and rescues the survival of both\n                    <jats:italic>C9ORF72<\/jats:italic>\n                    and sporadic ALS iMNs. Importantly, 3K3A-APC also lowers glutamate receptor levels and rescues proteostasis in vivo in\n                    <jats:italic>C9ORF72<\/jats:italic>\n                    gain- and loss-of-function mouse models. Thus, motor neurons from\n                    <jats:italic>C9ORF72<\/jats:italic>\n                    and at least a subset of sporadic ALS patients share early defects in autophagosome formation and glutamate receptor homeostasis and a single therapeutic approach may be efficacious against these disease processes.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.127736","type":"journal-article","created":{"date-parts":[[2019,7,16]],"date-time":"2019-07-16T12:01:21Z","timestamp":1563278481000},"source":"Crossref","is-referenced-by-count":49,"title":["Identification and therapeutic rescue of autophagosome and glutamate receptor defects in C9ORF72 and sporadic ALS neurons"],"prefix":"10.1172","volume":"4","author":[{"given":"Yingxiao","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA."},{"name":"Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, Los Angeles, California, USA."},{"name":"Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Ting","family":"Hung","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA."},{"name":"Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, Los Angeles, California, USA."},{"name":"Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Rocha","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology and Regenerative Medicine, Keck School 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