Exploration of Bromodomain Proteins as Drug Targets for Niemann–Pick Type C Disease
Abstract
1. Introduction
2. Results
2.1. Effects of JQ1 on Viability, Protein Levels of NPC1, and Its Distribution in Human Skin Fibroblasts
2.2. Effects of JQ1 on Lysosomes in Patient-Derived Skin Fibroblasts
2.3. Effects of JQ1 on Cholesterol Accumulation in Patient-Derived Skin Fibroblasts
2.4. Effects of JQ1 on Skin Fibroblasts from Different NPCD Patients
2.5. Effects of JQ1 on Cholesterol Accumulation in Patient-Derived Fibroblasts in the Presence of an NPC1 Inhibitor
2.6. Effects of JQ1 on HDAC Inhibitor-Mediated Reduction in Cholesterol Accumulation in Patient-Derived Fibroblasts
3. Discussion
4. Materials and Methods
4.1. Cell Culture and Drug Treatment
4.2. Cell Number and Viability
4.3. Lysate Preparation and Immunoblotting
4.4. Endoglycosidase H Assay
4.5. Immunocytochemical Staining
4.6. Cytochemical Staining
4.7. Lysotracker Staining and Cytometry
4.8. Hexosaminidase Activity Assay
4.9. Data Analysis and Visualization
5. Patents
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
Abbreviations
ANOVA | Analysis of variance |
BET | Bromodomain and extraterminal domain |
DMSO | Dimethylsulfoxide |
EndoH | Endoglycosidase H |
HDAC | Histone deacetylase |
NPCD | Niemann–Pick type C disease |
PBS | Phosphate-buffered saline |
ROIs | Regions of interest |
SAHA | Suberoylanilide hydroxamic acid |
U18 | 3-beta-[2-(diethylamine)ethoxy]androst-5-en-17-one |
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Parente, M.; Barthelemy, A.; Tonini, C.; Caputo, S.; Sacchi, A.; Leone, S.; Segatto, M.; Pfrieger, F.W.; Pallottini, V. Exploration of Bromodomain Proteins as Drug Targets for Niemann–Pick Type C Disease. Int. J. Mol. Sci. 2025, 26, 5769. https://doi.org/10.3390/ijms26125769
Parente M, Barthelemy A, Tonini C, Caputo S, Sacchi A, Leone S, Segatto M, Pfrieger FW, Pallottini V. Exploration of Bromodomain Proteins as Drug Targets for Niemann–Pick Type C Disease. International Journal of Molecular Sciences. 2025; 26(12):5769. https://doi.org/10.3390/ijms26125769
Chicago/Turabian StyleParente, Martina, Amélie Barthelemy, Claudia Tonini, Sara Caputo, Alessandra Sacchi, Stefano Leone, Marco Segatto, Frank W. Pfrieger, and Valentina Pallottini. 2025. "Exploration of Bromodomain Proteins as Drug Targets for Niemann–Pick Type C Disease" International Journal of Molecular Sciences 26, no. 12: 5769. https://doi.org/10.3390/ijms26125769
APA StyleParente, M., Barthelemy, A., Tonini, C., Caputo, S., Sacchi, A., Leone, S., Segatto, M., Pfrieger, F. W., & Pallottini, V. (2025). Exploration of Bromodomain Proteins as Drug Targets for Niemann–Pick Type C Disease. International Journal of Molecular Sciences, 26(12), 5769. https://doi.org/10.3390/ijms26125769