{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T07:28:14Z","timestamp":1793863694835,"version":"4.6.1"},"reference-count":23,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T00:00:00Z","timestamp":1753401600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2025,7,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Glaucoma and Alzheimer's disease (AD), two neurodegenerative disorders with potential mechanistic overlaps, share dysregulated pathways involving neuroinflammation and oxidative stress. This study investigates the neuroprotective role of S100A11, an S100 protein family member linked to NF\u2010\u03baB and antioxidant signaling, in both diseases. By integrating bioinformatics and experimental approaches, transcriptomic datasets (GSE27276 for glaucoma, GSE97760 for AD) were analyzed to identify shared differentially expressed genes (DEGs). Functional enrichment revealed DEG associations with neural conduction, neurotransmitter transport, and membrane function. In\u00a0vitro and in\u00a0vivo models demonstrated that S100A11 overexpression enhances cell proliferation, suppresses apoptosis, alleviates neuroinflammation and oxidative stress, and improves optic nerve and cognitive functions, mediated via NF\u2010\u03baB\/MAPK pathway modulation. Mendelian randomization (MR) analysis, leveraging GWAS data, found no causal link between four glaucoma subtypes (including POAG and PACG) and AD. Despite this, overlapping molecular mechanisms\u2014particularly S100A11\u2010driven regulation of neuroinflammatory and antioxidant responses\u2014suggest neural system dysregulation as a shared pathogenic hallmark. These findings position S100A11 as a dual therapeutic target for glaucoma and AD, bridging neurodegenerative processes through pathway\u2010specific neuroprotection. The study underscores the complexity of neurodegenerative comorbidities while highlighting S100A11's translational potential in mitigating cross\u2010disease pathology.<\/jats:p>","DOI":"10.1096\/fj.202500804r","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T13:32:38Z","timestamp":1753450358000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cross\u2010Talk Between Glaucoma and Alzheimer's Disease:\n                    <scp>S100A11<\/scp>\n                    as a Dual Regulator of Neurodegeneration Through Inflammation and Antioxidant Signaling"],"prefix":"10.1096","volume":"39","author":[{"given":"Lin","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Neurology The Affiliated Wenling Hospital of Wenzhou Medical University (The First People\u2019s Hospital of Wenling)  Wenling Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingyu","family":"Liang","sequence":"additional","affiliation":[{"name":"Jinzhou Medical University  Jinzhou Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5757-7367","authenticated-orcid":false,"given":"Manyu","family":"Li","sequence":"additional","affiliation":[{"name":"Liaoning Provincial Military Region Dalian 15th Retired Cadres Recuperation Center  Dalian Liaoning 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