{"doi":"10.3390/ijms26125827","title":"Dysregulation of Inositol Polyphosphate 5-Phosphatase OCRL in Alzheimer’s Disease: Implications for Autophagy Dysfunction","abstract":"Autophagy is impaired in Alzheimer’s disease (AD), particularly at the stage of autophagosome–lysosome 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.","journal":"International Journal of Molecular Sciences","year":2025,"id":526015,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9598,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1401535,"name":"May Thazin Htut","orcid":null,"position":1,"is_corresponding":false},{"id":1401536,"name":"Eugenia Maria Antonelli","orcid":null,"position":2,"is_corresponding":false},{"id":1401537,"name":"Andreea‐Claudia Kosa","orcid":null,"position":3,"is_corresponding":false},{"id":1401095,"name":"Lidia Lopez‐Gutierrez","orcid":"0000-0001-7631-0505","position":4,"is_corresponding":false},{"id":1401096,"name":"Carolina Quintanilla‐Sánchez","orcid":"0000-0002-0595-6162","position":5,"is_corresponding":false},{"id":1401538,"name":"Emmanuel Aydin","orcid":null,"position":6,"is_corresponding":false},{"id":1401539,"name":"Emilie Doeraene","orcid":null,"position":7,"is_corresponding":false},{"id":1401097,"name":"Siranjeevi Nagaraj","orcid":"0000-0001-8132-491X","position":8,"is_corresponding":false},{"id":303136,"name":"Ana Raquel Ramos","orcid":null,"position":9,"is_corresponding":false},{"id":882549,"name":"Katia Coulonval","orcid":"0000-0003-3799-569X","position":10,"is_corresponding":false},{"id":882552,"name":"Pierre P. Roger","orcid":"0000-0002-5812-1783","position":11,"is_corresponding":false},{"id":1401098,"name":"Jean‐Pierre Brion","orcid":"0000-0002-1917-775X","position":12,"is_corresponding":false},{"id":711761,"name":"Karelle Leroy","orcid":"0000-0002-8661-5262","position":13,"is_corresponding":false},{"id":1401094,"name":"Kunié Ando","orcid":"0000-0003-3822-175X","position":0,"is_corresponding":true}],"reference_count":98,"raw_metadata":null,"created_at":"2026-07-19T02:50:25.860105Z","pmid":"40565289","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}