{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:05:40Z","timestamp":1792638340620,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,1,3]],"date-time":"2024-01-03T00:00:00Z","timestamp":1704240000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007847","name":"Natural Science Foundation of Jilin Province","doi-asserted-by":"publisher","award":["YDZJ2023ZYTS468"],"award-info":[{"award-number":["YDZJ2023ZYTS468"]}],"id":[{"id":"10.13039\/100007847","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Extracellular elastin\u2010derived peptides (EDPs) accumulate in the aging brain and have been associated with vascular dementia and Alzheimer's disease (AD). The activation of inflammatory processes in glial cells with EDP treatment has received attention, but not in neurons. To properly understand EDPs' pathogenic significance, the impact on neuronal function and neuron\u2013microglia crosstalk was explored further. Among the EDP molecules, Val\u2010Gly\u2010Val\u2010Ala\u2010Pro\u2010Gly (VGVAPG) is a typical repeating hexapeptide. Here, we observed that EDPs\u2010VGVAPG influenced neuronal survival and morphology in a dose\u2010dependent manner. High concentrations of VGVAPG induced synapse loss and microglia hyperactivation in\u00a0vivo and in\u00a0vitro. Following EDP incubation, galectin 3 (Gal\u20103) released by neurons served as a chemokine, attracting microglial engulfment. Blocking Gal\u20103 and EDP binding remedied synapse loss in neurons and phagocytosis in microglia. In response to the accumulation of EDPs, proteomics in matrix remodeling and cytoskeleton dynamics, such as a disintegrin and metalloproteinase (ADAM) family, were engaged. These findings in extracellular EDPs provided more evidence for the relationship between aging and neuron dysfunction, increasing the insight of neuroinflammatory responses and the development of new specialized extracellular matrix remolding\u2010targeted therapy options for dementia or other neurodegenerative disease.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc16039-fig-0008-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  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