{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:16:43Z","timestamp":1790399803332,"version":"4.1.0"},"reference-count":123,"publisher":"American Society for Cell Biology (ASCB)","issue":"20","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:p>Synaptopathy underlying memory deficits in Alzheimer\u2019s disease (AD) is increasingly thought to be instigated by toxic oligomers of the amyloid beta peptide (A\u03b2Os). Given the long latency and incomplete penetrance of AD dementia with respect to A\u03b2 pathology, we hypothesized that factors present in the CNS may physiologically protect neurons from the deleterious impact of A\u03b2Os. Here we employed physically separated neuron\u2013astrocyte cocultures to investigate potential non\u2013cell autonomous neuroprotective factors influencing A\u03b2O toxicity. Neurons cultivated in the absence of an astrocyte feeder layer showed abundant A\u03b2O binding to dendritic processes and associated synapse deterioration. In contrast, neurons in the presence of astrocytes showed markedly reduced A\u03b2O binding and synaptopathy. Results identified the protective factors released by astrocytes as insulin and insulin-like growth factor-1 (IGF1). The protective mechanism involved release of newly bound A\u03b2Os into the extracellular medium dependent upon trafficking that was sensitive to exosome pathway inhibitors. Delaying insulin treatment led to A\u03b2O binding that was no longer releasable. The neuroprotective potential of astrocytes was itself sensitive to chronic A\u03b2O exposure, which reduced insulin\/IGF1 expression. Our findings support the idea that physiological protection against synaptotoxic A\u03b2Os can be mediated by astrocyte-derived insulin\/IGF1, but that this protection itself is vulnerable to A\u03b2O buildup.<\/jats:p>","DOI":"10.1091\/mbc.e17-06-0416","type":"journal-article","created":{"date-parts":[[2017,8,10]],"date-time":"2017-08-10T00:40:28Z","timestamp":1502325628000},"page":"2623-2636","source":"Crossref","is-referenced-by-count":83,"title":["Neuroprotective astrocyte-derived insulin\/insulin-like growth factor 1 stimulates endocytic processing and extracellular release of neuron-bound A\u03b2 oligomers"],"prefix":"10.1091","volume":"28","author":[{"given":"Jason","family":"Pitt","sequence":"first","affiliation":[{"name":"Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Evanston, IL 60208"},{"name":"Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle C.","family":"Wilcox","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Evanston, IL 60208"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Tortelli","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro RJ 21944-590, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luan Pereira","family":"Diniz","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro RJ 21944-590, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maira S.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro RJ 21944-590, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassandra","family":"Dobbins","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Evanston, IL 60208"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Wen","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sathwik","family":"Nandamuri","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Evanston, IL 60208"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fl\u00e1via C. 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