Role of DNA Methyl-CpG-Binding Protein MeCP2 in Rett Syndrome Pathobiology and Mechanism of Disease
Abstract
:1. Introduction to Rett Syndrome
2. History of Rett Syndrome
3. Clinical Features, Diagnosis, and Histopathology of RTT
Gross and Microscopic Features of RTT
4. Genetic Basis of Rett Syndrome: Link between Genotype and Phenotype
4.1. Mutations in the N-Terminal Domain
4.2. Mutations in the Methyl-CpG-Binding Domain
4.3. Mutations in the Intervening Domain
4.4. Mutations in the Transcriptional Repression Domain
4.5. Mutations in the C-Terminal Domain
5. Biological Systems to Study Rett Syndrome
6. Epigenetic Regulation Mechanisms and Role in Controlling MeCP2 Homeostasis Network
6.1. Chromatin Remodelling
6.2. Histone Post-Translational Modifications
6.3. Noncoding RNAs
6.4. DNA Methylation
6.5. Writers of DNA Methylation
6.6. Erasers of DNA Methylation
6.7. Methyl-CpG-Binding Protein Family
6.8. MECP2/Mecp2 Gene Structure and MeCP2 Protein
6.9. MeCP2 Expression and Regulation
7. MeCP2 Target Genes: A Focus on BDNF and Its Related Signaling Cascades
7.1. Brain-Derived Neurotrophic Factor
7.1.1. BDNF Signaling
7.1.2. BDNF/Bdnf Regulation
7.1.3. Role of MeCP2 in BDNF Regulation
7.1.4. BDNF and Pathophysiology of RTT
7.1.5. BDNF and Cellular Origin of Detection in the Human Brain
7.2. MicroRNAs
7.2.1. Role of miRNAs in Central Nervous System Development
7.2.2. The Role of miR132 and its Effects on Neural Structure and Function
7.2.3. Homeostatic Regulation of MeCP2 by miR132
8. Lessons Learned from the Human Brain on MeCP2-BDNF-miR132 homeostasis Regulatory Components
9. Therapeutic Strategies for RTT
9.1. Molecular Treatments and Gene Dosage Concerns
9.2. Activating MECP2 on the Inactive X-Chromosome
9.3. Gene-Editing Strategies
9.4. Challenges of Protein Replacement
9.5. Targeting Downstream Signaling Pathways of MeCP2
9.6. Clinical Trials
10. Closing Remarks
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Pejhan, S.; Rastegar, M. Role of DNA Methyl-CpG-Binding Protein MeCP2 in Rett Syndrome Pathobiology and Mechanism of Disease. Biomolecules 2021, 11, 75. https://doi.org/10.3390/biom11010075
Pejhan S, Rastegar M. Role of DNA Methyl-CpG-Binding Protein MeCP2 in Rett Syndrome Pathobiology and Mechanism of Disease. Biomolecules. 2021; 11(1):75. https://doi.org/10.3390/biom11010075
Chicago/Turabian StylePejhan, Shervin, and Mojgan Rastegar. 2021. "Role of DNA Methyl-CpG-Binding Protein MeCP2 in Rett Syndrome Pathobiology and Mechanism of Disease" Biomolecules 11, no. 1: 75. https://doi.org/10.3390/biom11010075