Dysregulation of Inositol Polyphosphate 5-Phosphatase OCRL in Alzheimer’s Disease: Implications for Autophagy Dysfunction
Abstract
1. Introduction
2. Results
2.1. OCRL Protein Accumulates in Dystrophic Neurites in AD Brains
2.2. RNA Levels, Protein Solubility, and Post-Translational Modifications (PTMs) of OCRL in AD Brains
2.2.1. RNA Expression Levels of OCRL and the Autophagy Marker BECN1 Are Not Significantly Altered in AD Brains
2.2.2. OCRL Is Depleted from the RIPA-Soluble Fraction and Correlates with Beclin1 Levels in Control and AD Brains
2.2.3. No Aberrant Post-Translational Modifications of OCRL Were Detected in AD Samples by 2D WB
2.3. OCRL Overexpression Attenuates FRET-Positive Tau Inclusions in HEK Tau RD P301L FRET Biosensor Cells
3. Discussion
4. Materials and Methods
4.1. Antibodies
4.2. Human Brain Tissues
4.3. Preparation of Brain Homogenates for Biochemical Analysis
4.4. Preparation of Human Sarkosyl Insoluble PHF-Tau Fraction
4.5. Analyses of RNA Expressions Human and Mouse Data Sets
4.6. WB
4.7. Mouse Lines
4.8. Immunohistochemistry
4.9. Cell Culture
4.10. Liposome-Mediated Transduction of Sarkosyl Insoluble Fraction Containing AD-PHF in Tau RD P301S FRET Biosensor Cells
4.11. Fluorescence-Activated Cell Sorting (FACS)
4.12. Fixation and Counterstaining of Tau RD P301S FRET Biosensor Cells
4.13. Statistical Analyses
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Ando, K.; Thazin Htut, M.; Antonelli, E.M.; Kosa, A.-C.; Lopez-Gutierrez, L.; Quintanilla-Sánchez, C.; Aydin, E.; Doeraene, E.; Nagaraj, S.; Ramos, A.R.; et al. Dysregulation of Inositol Polyphosphate 5-Phosphatase OCRL in Alzheimer’s Disease: Implications for Autophagy Dysfunction. Int. J. Mol. Sci. 2025, 26, 5827. https://doi.org/10.3390/ijms26125827
Ando K, Thazin Htut M, Antonelli EM, Kosa A-C, Lopez-Gutierrez L, Quintanilla-Sánchez C, Aydin E, Doeraene E, Nagaraj S, Ramos AR, et al. Dysregulation of Inositol Polyphosphate 5-Phosphatase OCRL in Alzheimer’s Disease: Implications for Autophagy Dysfunction. International Journal of Molecular Sciences. 2025; 26(12):5827. https://doi.org/10.3390/ijms26125827
Chicago/Turabian StyleAndo, Kunie, May Thazin Htut, Eugenia Maria Antonelli, Andreea-Claudia Kosa, Lidia Lopez-Gutierrez, Carolina Quintanilla-Sánchez, Emmanuel Aydin, Emilie Doeraene, Siranjeevi Nagaraj, Ana Raquel Ramos, and et al. 2025. "Dysregulation of Inositol Polyphosphate 5-Phosphatase OCRL in Alzheimer’s Disease: Implications for Autophagy Dysfunction" International Journal of Molecular Sciences 26, no. 12: 5827. https://doi.org/10.3390/ijms26125827
APA StyleAndo, K., Thazin Htut, M., Antonelli, E. M., Kosa, A.-C., Lopez-Gutierrez, L., Quintanilla-Sánchez, C., Aydin, E., Doeraene, E., Nagaraj, S., Ramos, A. R., Coulonval, K., Roger, P. P., Brion, J.-P., & Leroy, K. (2025). Dysregulation of Inositol Polyphosphate 5-Phosphatase OCRL in Alzheimer’s Disease: Implications for Autophagy Dysfunction. International Journal of Molecular Sciences, 26(12), 5827. https://doi.org/10.3390/ijms26125827