c-Abl/TFEB Pathway Activation as a Common Pathogenic Mechanism in Lysosomal Storage Diseases: Therapeutic Potential of c-Abl Inhibitors
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Cultures and Treatments
2.2. Plasmids and Transfection
2.3. Immunofluorescence Staining
2.4. Filipin Staining
2.5. Western Blotting
2.6. Statistical Analysis
3. Results
3.1. The Inhibition of c-Abl Induces TFEB Nuclear Localization in Gaucher, Niemann-Pick Type A, and Niemann-Pick Type C Neuronal Models
3.2. TFEB Tyr173 Is Relevant for Its Cytoplasmic Retention Mediated by c-Abl
3.3. The Inhibition of c-Abl Induces Cellular Clearance of Cholesterol in Gaucher, Niemann-Pick Type A, and Niemann-Pick Type C Neuronal Models
3.4. α-TOH Inhibits c-Abl Activation and Induces TFEB Nuclear Translocation in an NPC HeLa Model
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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TFEB | Sequence | Y75 | Y100 | Y173 | Y194 | Y413 |
---|---|---|---|---|---|---|
Wild Type (WT) | Aa | QSYLE | ETYGN | LGYIN | NVYSS | PGYPE |
Codon | CAGTCCTACCTGGAG | GAGACCTATGGGAAC | CTTGGCTACATCAAT | AATGTGTACAGCAGC | CCGGGCTACCCCGAA | |
Phosphomimetic Y173 | Aa | QSYLE | ETYGN | LGEIN | NVYSS | PGYPE |
Codon | CAGTCCTACCTGGAG | GAGACCTATGGGAAC | CTTGGCGAGATCAAT | AATGTGTACAGCAGC | CCGGGCTACCCCGAA | |
All mutated except Y173 | Aa | QSFLE | ETFGN | LGYIN | NVFSS | PGFPE |
Codon | CAGTCCTTCCTGGAG | GAGACCTTCGGGAAC | CTTGGCTACATCAAT | AATGTGTTCAGCAGC | CCGGGCTTCCCCGAA | |
All mutated | Aa | QSFLE | ETFGN | LGFIN | NVFSS | PGFPE |
Codon | CAGTCCTTCCTGGAG | GAGACCTTCGGGAAC | CTTGGCTTCATCAAT | AATGTGTTCAGCAGC | CCGGGCTTCCCCGAA | |
All mutated except Y75 | Aa | QSYLE | ETFGN | LGFIN | NVFSS | PGFPE |
Codon | CAGTCCTACCTGGAG | GAGACCTTCGGGAAC | CTTGGCTTCATCAAT | AATGTGTTCAGCAGC | CCGGGCTTCCCCGAA | |
Mutated only Y173 | Aa | QSYLE | ETYGN | LGFIN | NVYSS | PGYPE |
Codon | CAGTCCTACCTGGAG | GAGACCTATGGGAAC | CTTGGCTTCATCAAT | AATGTGTACAGCAGC | CCGGGCTACCCCGAA |
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Guerra, M.V.; Castro, J.; Moreno, A.; Balboa, E.; Marugan, J.J.; Alvarez, A.R.; Zanlungo, S. c-Abl/TFEB Pathway Activation as a Common Pathogenic Mechanism in Lysosomal Storage Diseases: Therapeutic Potential of c-Abl Inhibitors. Antioxidants 2025, 14, 611. https://doi.org/10.3390/antiox14050611
Guerra MV, Castro J, Moreno A, Balboa E, Marugan JJ, Alvarez AR, Zanlungo S. c-Abl/TFEB Pathway Activation as a Common Pathogenic Mechanism in Lysosomal Storage Diseases: Therapeutic Potential of c-Abl Inhibitors. Antioxidants. 2025; 14(5):611. https://doi.org/10.3390/antiox14050611
Chicago/Turabian StyleGuerra, Miguel V., Juan Castro, Antonio Moreno, Elisa Balboa, Juan J. Marugan, Alejandra R. Alvarez, and Silvana Zanlungo. 2025. "c-Abl/TFEB Pathway Activation as a Common Pathogenic Mechanism in Lysosomal Storage Diseases: Therapeutic Potential of c-Abl Inhibitors" Antioxidants 14, no. 5: 611. https://doi.org/10.3390/antiox14050611
APA StyleGuerra, M. V., Castro, J., Moreno, A., Balboa, E., Marugan, J. J., Alvarez, A. R., & Zanlungo, S. (2025). c-Abl/TFEB Pathway Activation as a Common Pathogenic Mechanism in Lysosomal Storage Diseases: Therapeutic Potential of c-Abl Inhibitors. Antioxidants, 14(5), 611. https://doi.org/10.3390/antiox14050611