{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T17:06:52Z","timestamp":1789578412039,"version":"build-2803163510"},"reference-count":91,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T00:00:00Z","timestamp":1782000000000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012151","name":"Sanming Project of Medicine in Shenzhen","doi-asserted-by":"publisher","award":["SZSM202411007"],"award-info":[{"award-number":["SZSM202411007"]}],"id":[{"id":"10.13039\/501100012151","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp; Disease"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To systematically review the structural features of secreted frizzled\u2011related protein 5 (SFRP5) and its dual regulation of canonical\/non\u2011canonical Wnt signaling, analyze its association with metabolic disorders, and specifically explore the role and mechanisms of the SFRP5\u2013lipid metabolism axis in neural and optic nerve development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic literature search was performed to review the molecular structure of SFRP5, its regulation of Wnt pathways, and its relationship with metabolic dysregulation. The mechanisms by which SFRP5 modulates the microglia\/astrocyte\u2011mediated neuroimmune microenvironment, myelination, synaptic plasticity, and neuronal mitochondrial energy homeostasis were analyzed, and current therapeutic strategies targeting the SFRP5 network were summarized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SFRP5 participates in normal central nervous system development by shaping the neuroimmune microenvironment, promoting myelination, regulating synaptic plasticity, and maintaining mitochondrial energy balance. Under obese and diabetic conditions, downregulation of SFRP5 leads to overactivation of Wnt5a\/JNK signaling, resulting in lipid metabolic disturbances and neuroinflammation. These changes share common pathological features with neurodevelopmental disorders such as autism spectrum disorder, intellectual disability, optic nerve hypoplasia, and retinal vascular dysplasia. The SFRP5\u2013lipid metabolism axis plays a critical role in neural and optic nerve development, and its dysregulation underlies the neuropathology associated with metabolic diseases. Therapeutic interventions explored to date\u2014including recombinant protein, gene therapy, small\u2011molecule activators, and acupuncture\u2014have shown promising potential.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The SFRP5\u2013lipid metabolism axis represents a key link connecting metabolic disorders with neurodevelopmental abnormalities. Future research should focus on spatiotemporal specificity at single\u2011cell resolution, elucidation of gene\u2013environment interactions, and the development of efficient central nervous system delivery systems, thereby providing new avenues for the prevention and treatment of neural and optic nerve developmental abnormalities.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/iid3.70469","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T03:17:14Z","timestamp":1782098234000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Research Progress on Anti\u2010Inflammatory Adipokine SFRP5\u2010Mediated Lipid Metabolism and Its Potential Role in Neural Development"],"prefix":"10.1002","volume":"14","author":[{"given":"Qianfang","family":"Jia","sequence":"first","affiliation":[{"name":"The First Clinical Medical College Zhejiang Chinese Medical University Hangzhou 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