Understanding the Role of the SMN Complex Component GEMIN5 and Its Functional Relationship with Demethylase KDM6B in the Flunarizine-Mediated Neuroprotection of Motor Neuron Disease Spinal Muscular Atrophy
Abstract
:1. Introduction
2. Results
2.1. SMN-Complex Component Gemin5 Expression Levels Are Modulated by Flunarizine
2.2. Expression of Key Motor Neuron Genes Is Modulated by Flunarizine
2.3. Flunarizine-Modulated Transcripts Are Immunoprecipitated by GEMIN5
2.4. Gemin5 Depletion Mimics the Early Time Point of Flunarizine Treatment
2.5. Neurite Outgrowth Is Promoted in Cell Cultures by Flunarizine
2.6. Flunarizine Stimulates KDM6B and HB9 Expression in Motor Neurons of Smn-Deficient Mice
3. Discussion
4. Materials and Methods
4.1. Cell Cultures, Flunarizine Treatment, and Immunodetection
4.2. Neurite Tracking with IncuCyte®
4.3. Transfection Assays
4.4. Immunoblotting Analysis
4.5. RNA Extraction and Expression Analysis
4.6. RNA Immunoprecipitation
4.7. Animal Procedure and Spinal Cord Tissue Experiment
4.8. Immunofluorescence Microscopy, Image Acquisition, Processing, and Analysis
4.9. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Salman, B.; Bon, E.; Delers, P.; Cottin, S.; Pasho, E.; Ciura, S.; Sapaly, D.; Lefebvre, S. Understanding the Role of the SMN Complex Component GEMIN5 and Its Functional Relationship with Demethylase KDM6B in the Flunarizine-Mediated Neuroprotection of Motor Neuron Disease Spinal Muscular Atrophy. Int. J. Mol. Sci. 2024, 25, 10039. https://doi.org/10.3390/ijms251810039
Salman B, Bon E, Delers P, Cottin S, Pasho E, Ciura S, Sapaly D, Lefebvre S. Understanding the Role of the SMN Complex Component GEMIN5 and Its Functional Relationship with Demethylase KDM6B in the Flunarizine-Mediated Neuroprotection of Motor Neuron Disease Spinal Muscular Atrophy. International Journal of Molecular Sciences. 2024; 25(18):10039. https://doi.org/10.3390/ijms251810039
Chicago/Turabian StyleSalman, Badih, Emeline Bon, Perrine Delers, Steve Cottin, Elena Pasho, Sorana Ciura, Delphine Sapaly, and Suzie Lefebvre. 2024. "Understanding the Role of the SMN Complex Component GEMIN5 and Its Functional Relationship with Demethylase KDM6B in the Flunarizine-Mediated Neuroprotection of Motor Neuron Disease Spinal Muscular Atrophy" International Journal of Molecular Sciences 25, no. 18: 10039. https://doi.org/10.3390/ijms251810039