{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T10:30:51Z","timestamp":1787135451360,"version":"build-2736575974"},"reference-count":191,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32501138, 82370592, 32401063"],"award-info":[{"award-number":["32501138, 82370592, 32401063"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017596","name":"Natural Science Basic Research Program of Shaanxi Province","doi-asserted-by":"publisher","award":["2025JC-YBQN-1132"],"award-info":[{"award-number":["2025JC-YBQN-1132"]}],"id":[{"id":"10.13039\/501100017596","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013101","name":"Scientific Research Plan Projects of Shaanxi Education Department","doi-asserted-by":"publisher","award":["25JK0659"],"award-info":[{"award-number":["25JK0659"]}],"id":[{"id":"10.13039\/501100013101","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    \u03b12-3-sialylated glycosphingolipids (\u03b12-3-GSLs) are major constituents of neuronal membranes and lipid rafts, where they shape receptor compartmentalization, signal-complex assembly, and cell-cell communication. Their biological effects, however, vary by molecular subtype, cell type, disease stage, concentration, and local microenvironment. This review synthesizes evidence on spatiotemporal alterations in \u03b12-3-GSL profiles and their relationships to neuroinflammation, immune responses, proteostasis, and programmed cell death across Parkinson\u2019s disease, Alzheimer\u2019s disease, Huntington\u2019s disease, multiple sclerosis, and Guillain\u2013Barr\u00e9 syndrome. Particular attention is given to GM1, GD1a, and GD3 and to mechanisms involving TLR4\/NF-\u03baB, PI3K\/AKT, autophagy-lysosomal function, complement, damage-associated molecular patterns (DAMPs) recognition, and death-receptor signaling. Evidence is stratified into relatively well-supported, model-specific or incomplete, and conceptually inferred mechanisms. On this basis, we propose a lipid\u2013inflammation\u2013immunity\u2013cell death framework that organizes potentially shared downstream processes while explicitly retaining disease-specific differences. This framework is not a validated universal causal pathway; rather, it provides an analytical structure for identifying evidence gaps and testable hypotheses. Disease-specific and parallel cross-disease studies, coupled with spatial lipidomics,\n                    <jats:italic>in vivo<\/jats:italic>\n                    tracing, and subtype-selective interventions, will be required to determine when \u03b12-3-GSL manipulation is protective, neutral, or harmful and to support rational clinical translation.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1865721","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T10:19:55Z","timestamp":1787134795000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["\u03b12-3-sialylated glycosphingolipids in neuroinflammation, immunity, and programmed cell death: mechanistic evidence and context-dependent regulation: a comprehensive review"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiaocheng","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Basic Medical Sciences, Xi\u2019an Medical University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Electrophysiology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University","place":["Weihai, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinmeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, Xi\u2019an Medical University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujin","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, Xi\u2019an Medical University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanting","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, Xi\u2019an 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