MG53 Preserves Neuromuscular Junction Integrity and Alleviates ALS Disease Progression
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animal Models
2.2. Isolation of Single Live FDB Muscle Fibers (Myofibers)
2.3. Confocal Imaging and Image Analysis
2.4. Imaging of T-Tubule Network Integrity and Mitochondrial Membrane Potential at NMJ
2.5. Evaluation of Mitochondrial ROS Level in Live FDB Myofibers
2.6. Evaluation of Membrane Repair Function in FDB Myofibers
2.7. Quantification of Membrane Integrity of Diaphragm Muscle
2.8. Immunohistochemistry of Mouse and Human Muscle
2.9. Immunoblotting Assay
2.10. Evaluation of Serum Creatine Kinase (CK) Activity
2.11. Quantification of Motor Neurons in Lumbar Spinal Cord with Nissl Staining
2.12. PEGylation of rhMG53
2.13. Pharmacokinetic Evaluation of PEG–rhMG53 in Rats
2.14. Intravenous Administration of rhMG53 and PEG–rhMG53
2.15. Numerical Data Presentation and Statistics
3. Results
3.1. Increased Susceptibility to Diaphragm Injury Is an Early Pathology Event in SOD1(G93A) Mice
3.2. MG53 Is Implicated in the Membrane Fragility of G93A Diaphragm, Fast- and Slow-Type Muscles
3.3. NMJ Is an Active Site of Injury Repair by MG53 that Is Lost in ALS
3.4. Mitochondrial Dysfunction Is Associated with the Disruption of Cell Membrane Integrity at NMJs of the ALS Muscle
3.5. Impaired MG53 Membrane Repair Function Is a Common Pathological Feature of ALS Muscle
3.6. Recombinant Human MG53 Protein Preserves Membrane Integrity of Diaphragm in G93A Mice
3.7. Systemic Application of rhMG53 Preserves NMJ Integrity and Extends Life Span of G93A Mice
4. Discussion
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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Yi, J.; Li, A.; Li, X.; Park, K.; Zhou, X.; Yi, F.; Xiao, Y.; Yoon, D.; Tan, T.; Ostrow, L.W.; et al. MG53 Preserves Neuromuscular Junction Integrity and Alleviates ALS Disease Progression. Antioxidants 2021, 10, 1522. https://doi.org/10.3390/antiox10101522
Yi J, Li A, Li X, Park K, Zhou X, Yi F, Xiao Y, Yoon D, Tan T, Ostrow LW, et al. MG53 Preserves Neuromuscular Junction Integrity and Alleviates ALS Disease Progression. Antioxidants. 2021; 10(10):1522. https://doi.org/10.3390/antiox10101522
Chicago/Turabian StyleYi, Jianxun, Ang Li, Xuejun Li, Kiho Park, Xinyu Zhou, Frank Yi, Yajuan Xiao, Dosuk Yoon, Tao Tan, Lyle W. Ostrow, and et al. 2021. "MG53 Preserves Neuromuscular Junction Integrity and Alleviates ALS Disease Progression" Antioxidants 10, no. 10: 1522. https://doi.org/10.3390/antiox10101522
APA StyleYi, J., Li, A., Li, X., Park, K., Zhou, X., Yi, F., Xiao, Y., Yoon, D., Tan, T., Ostrow, L. W., Ma, J., & Zhou, J. (2021). MG53 Preserves Neuromuscular Junction Integrity and Alleviates ALS Disease Progression. Antioxidants, 10(10), 1522. https://doi.org/10.3390/antiox10101522