{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T06:28:18Z","timestamp":1792477698696,"version":"4.5.0"},"reference-count":55,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"48","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2024,11,29]]},"abstract":"<jats:p>Astrocyte secreted signals substantially affect disease pathology in neurodegenerative diseases. It remains little understood about how proinflammatory cytokines, such as interleukin-1\u03b1\/tumor necrosis factor\u2013\u03b1\/C1q (ITC), often elevated in neurodegenerative diseases, alter astrocyte-secreted signals and their effects in disease pathogenesis. By selectively isolating astrocyte exosomes (A-Exo.) and employing cell type\u2013specific exosome reporter mice, our current study showed that ITC cytokines significantly reduced A-Exo. secretion and decreased spreading of focally labeled A-Exo. in diseased SOD1G93A mice. Our results also found that A-Exo. were minimally associated with misfolded SOD1 and elicited no toxicity to mouse spinal and human iPSC\u2013derived motor neurons. In contrast, A-Exo. were neuroprotective against excitotoxicity, which was completely diminished by ITC cytokines and partially abolished by SOD1G93A expression. Subsequent proteomic characterization of A-Exo. and genetic analysis identified that surface expression of glial-specific HepaCAM preferentially mediates A-Exo\u2019s axon protection effect. Together, our study defines a cytokine-induced loss-of-function mechanism of A-Exo. in protecting neurons from excitotoxicity in amyotrophic lateral sclerosis.<\/jats:p>","DOI":"10.1126\/sciadv.adq3350","type":"journal-article","created":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T14:01:25Z","timestamp":1732716085000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":11,"title":["Inflammatory cytokines disrupt astrocyte exosomal HepaCAM-mediated protection against neuronal excitotoxicity in the SOD1G93A ALS model"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5689-841X","authenticated-orcid":true,"given":"Shijie","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Tufts University School of Medicine, Boston, MA 02111, 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