{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:21:54Z","timestamp":1792131714568,"version":"4.4.0"},"reference-count":97,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:00:00Z","timestamp":1750204800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Belgian Fondation Recherche Alzheimer\/Stichting Alzheimer Onderzoek","award":["T.0023.15"],"award-info":[{"award-number":["T.0023.15"]}]},{"name":"Belgian FRS-FNRS","award":["T.0023.15"],"award-info":[{"award-number":["T.0023.15"]}]},{"name":"Belgian Fonds de la Recherche Scientifique M\u00e9dicale","award":["T.0023.15"],"award-info":[{"award-number":["T.0023.15"]}]},{"name":"Fund Aline (King Baudouin Foundation)","award":["T.0023.15"],"award-info":[{"award-number":["T.0023.15"]}]},{"name":"ULB G\u00e9nicot Fund","award":["T.0023.15"],"award-info":[{"award-number":["T.0023.15"]}]},{"name":"Fondation M\u00e9dicale Reine Elisabeth","award":["T.0023.15"],"award-info":[{"award-number":["T.0023.15"]}]},{"name":"Academic Medical Interdisciplinary Research (AMIR) Foundation","award":["T.0023.15"],"award-info":[{"award-number":["T.0023.15"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Autophagy is impaired in Alzheimer\u2019s disease (AD), particularly at the stage of autophagosome\u2013lysosome fusion. Recent studies suggest that the inositol polyphosphate 5-phosphatase OCRL (Lowe oculocerebrorenal syndrome protein) is involved in this fusion process; however, its role in AD pathophysiology remains largely unclear. In this study, we investigated the localization and expression of OCRL in post-mortem AD brains and in a 5XFAD transgenic mouse model. While OCRL RNA levels were not significantly altered, OCRL protein was markedly reduced in the RIPA-soluble fraction and positively correlated with the autophagy marker Beclin1. Immunohistochemical analysis revealed OCRL immunoreactivity in neuronal cytoplasm, granulovacuolar degeneration bodies, and plaque-associated dystrophic neurites in AD brains. Furthermore, OCRL overexpression in a FRET-based tau biosensor cell model significantly reduced the tau-seeding-induced FRET signal. These findings suggest that OCRL dysregulation may contribute to autophagic deficits and the progression of tau pathology in AD.<\/jats:p>","DOI":"10.3390\/ijms26125827","type":"journal-article","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T04:08:06Z","timestamp":1750219686000},"page":"5827","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Dysregulation of Inositol Polyphosphate 5-Phosphatase OCRL in Alzheimer\u2019s Disease: Implications for Autophagy Dysfunction"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3822-175X","authenticated-orcid":false,"given":"Kunie","family":"Ando","sequence":"first","affiliation":[{"name":"Alzheimer and Other Tauopathies Research Group, ULB Neuroscience Institute (UNI), ULB Center for Diabetes Research (UCDR), Faculty of Medicine, Universit\u00e9 Libre de Bruxelles, 808 Route de Lennik, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"May","family":"Thazin Htut","sequence":"additional","affiliation":[{"name":"Alzheimer and Other Tauopathies Research Group, ULB Neuroscience Institute (UNI), ULB Center for Diabetes Research (UCDR), Faculty of Medicine, Universit\u00e9 Libre de Bruxelles, 808 Route de Lennik, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenia Maria","family":"Antonelli","sequence":"additional","affiliation":[{"name":"Alzheimer and Other Tauopathies Research Group, ULB Neuroscience Institute (UNI), ULB Center for Diabetes Research (UCDR), Faculty of Medicine, Universit\u00e9 Libre de Bruxelles, 808 Route de Lennik, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea-Claudia","family":"Kosa","sequence":"additional","affiliation":[{"name":"Alzheimer and Other Tauopathies Research Group, ULB Neuroscience Institute (UNI), ULB Center for Diabetes Research (UCDR), Faculty of Medicine, Universit\u00e9 Libre de Bruxelles, 808 Route de Lennik, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7631-0505","authenticated-orcid":false,"given":"Lidia","family":"Lopez-Gutierrez","sequence":"additional","affiliation":[{"name":"Alzheimer and Other Tauopathies Research Group, ULB Neuroscience Institute (UNI), ULB Center for Diabetes Research (UCDR), Faculty of Medicine, Universit\u00e9 Libre de Bruxelles, 808 Route de Lennik, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Quintanilla-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Alzheimer and Other Tauopathies Research Group, ULB Neuroscience Institute (UNI), ULB Center for Diabetes Research (UCDR), Faculty of Medicine, Universit\u00e9 Libre de Bruxelles, 808 Route de Lennik, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Aydin","sequence":"additional","affiliation":[{"name":"Alzheimer and Other Tauopathies Research Group, ULB Neuroscience Institute (UNI), ULB Center for Diabetes Research (UCDR), Faculty of Medicine, Universit\u00e9 Libre de Bruxelles, 808 Route de Lennik, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Doeraene","sequence":"additional","affiliation":[{"name":"Alzheimer and Other Tauopathies Research Group, ULB Neuroscience Institute (UNI), ULB Center for Diabetes Research (UCDR), Faculty of Medicine, Universit\u00e9 Libre de Bruxelles, 808 Route de Lennik, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siranjeevi","family":"Nagaraj","sequence":"additional","affiliation":[{"name":"Alzheimer and Other Tauopathies Research Group, ULB Neuroscience Institute (UNI), ULB Center for Diabetes Research (UCDR), Faculty of Medicine, Universit\u00e9 Libre de Bruxelles, 808 Route de Lennik, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Raquel","family":"Ramos","sequence":"additional","affiliation":[{"name":"IRIBHM-Jacques E. 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