Dysregulation of Inositol Polyphosphate 5-Phosphatase OCRL in Alzheimer’s Disease: Implications for Autophagy Dysfunction
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 <i>OCRL</i> 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.
Authors
- May Thazin Htut
- Carolina Quintanilla‐Sánchez (ORCID: https://orcid.org/0000-0002-0595-6162)
- Kunié Ando (ORCID: https://orcid.org/0000-0003-3822-175X)
- Lidia Lopez‐Gutierrez (ORCID: https://orcid.org/0000-0001-7631-0505)
- Siranjeevi Nagaraj (ORCID: https://orcid.org/0000-0001-8132-491X)
- Andreea‐Claudia Kosa
- Karelle Leroy (ORCID: https://orcid.org/0000-0002-8661-5262)
- Katia Coulonval (ORCID: https://orcid.org/0000-0003-3799-569X)
- Jean‐Pierre Brion (ORCID: https://orcid.org/0000-0002-1917-775X)
- Emilie Doeraene
- Pierre P. Roger
- Ana Raquel Ramos
- Emmanuel Aydin
- Eugenia Maria Antonelli
Institutions
- Université Libre de Bruxelles (BE)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2025-06-18
- DOI
- https://doi.org/10.3390/ijms26125827
- Citations
- 1
- Primary Topic
- Autophagy in Disease and Therapy
- Type
- article
- Field-Weighted Citation Impact
- 1.35
Funders
- University of Miami
- University of Pennsylvania
- Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques
- University of Pittsburgh
- Rush University
- Fonds De La Recherche Scientifique - FNRS
- China Scholarship Council
- Centre Hospitalier Régional Universitaire de Montpellier
- Université de Liège
- Koning Boudewijnstichting
- Association France Parkinson
- Centre Hospitalier Universitaire de Rennes
- Fondation pour la Recherche sur Alzheimer
- Fondation Médicale Reine Elisabeth
- National Institutes of Health
- National Institute on Aging
- Institute of Genetics