{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:59:35Z","timestamp":1790625575274,"version":"4.1.0"},"reference-count":82,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T00:00:00Z","timestamp":1753833600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["RC2788872"],"award-info":[{"award-number":["RC2788872"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Recent findings highlight that Reelin, a glycoprotein involved in neural development, synaptic plasticity, and neuroinflammation, plays some specific roles in neurodegenerative disorders associated with aging, such as age-related macular degeneration (AMD) and Alzheimer\u2019s disease (AD). Reelin modulates synaptic function and guarantees homeostasis in neuronal-associated organs\/tissues (brain and retina). The expression of Reelin is dysregulated in these neurological disorders, showing common pathways depending on chronic neurogenic inflammation and\/or dysregulation of the extracellular matrix in which Reelin plays outstanding roles. Recently, the relationship between AMD and AD has gained increasing attention as they share many common risk factors (aging, genetic\/epigenetic background, smoking, and malnutrition) and histopathological lesions, supporting certain pathophysiological crosstalk between these two diseases, especially regarding neuroinflammation, oxidative stress, and vascular complications. Outside the nervous system, Reelin is largely produced at the gastrointestinal epithelial level, in close association with innervated regions. The expression of Reelin receptors inside the gut suggests interesting aspects in the field of the gut\u2013brain\u2013eye axis, as dysregulation of the intestinal microbiota has been frequently described in neurodegenerative and behavioral disorders (AD, autism, and anxiety and\/or depression), most probably linked to inflammatory, neurogenic mediators, including Reelin. Herein we examined previous and recent findings on Reelin and neurodegenerative disorders, offering findings on Reelin\u2019s potential relation with the gut\u2013brain and gut\u2013brain\u2013eye axes and providing novel attractive hypotheses on the gut\u2013brain\u2013eye link through neuromodulator and microbiota interplay. Neurodegenerative disorders will represent the ground for a future starting point for linking the common neurodegenerative biomarkers (\u03b2-amyloid and tau) and the new proteins probably engaged in counteracting neurodegeneration and synaptic loss.<\/jats:p>","DOI":"10.3390\/ijms26157352","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T07:37:23Z","timestamp":1753861043000},"page":"7352","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Biomolecular Aspects of Reelin in Neurodegenerative Disorders: An Old Candidate for a New Linkage of the Gut\u2013Brain\u2013Eye Axis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2254-1647","authenticated-orcid":false,"given":"Bijorn Omar","family":"Balzamino","sequence":"first","affiliation":[{"name":"Research and Development Laboratory for Biochemical, Molecular and Cellular Applications in Ophthalmological Sciences, IRCCS-Fondazione Bietti, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1327-7642","authenticated-orcid":false,"given":"Filippo","family":"Biamonte","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico A. Gemelli IRCCS-CeMAD Translational Research Laboratories-Digestive Disease Center CeMAD, Department of Medical and Surgical Sciences, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9375-6071","authenticated-orcid":false,"given":"Alessandra","family":"Micera","sequence":"additional","affiliation":[{"name":"Research and Development Laboratory for Biochemical, Molecular and Cellular Applications in Ophthalmological Sciences, IRCCS-Fondazione Bietti, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Joly-Amado, A., Kulkarni, N., and Nash, K.R. (2023). Reelin Signaling in Neurodevelopmental Disorders and Neurodegenerative Diseases. 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