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Table of contents
Table of Contents
LIST OF FIGURES AND TABLES
LIST OF ABBREVIATIONS
INTRODUCTION
1. CHAPTER: THE SKELETAL MUSCLE
1.1 General introduction
1.2 Structure of muscle tissue
1.3 Muscle fibers and properties
1.3.1 Contractile properties
1.3.2 Metabolic properties
1.4 Glucose and lipid metabolism of skeletal muscle
1.4.1 The anaerobic metabolic pathway in muscle
1.4.2 The aerobic metabolic pathway in muscle
1.4.3 The PPAR signaling and metabolism
1.4.4 Targets of the PPARs
1.5 Regulation of muscle mass
1.5.1 Muscle atrophy
1.5.2 Muscle hypertrophy
1.6 Muscle regeneration
1.7 Response of skeletal muscle to repetitive muscle damage
2. CHAPTER: DUCHENNE MUSCULAR DYSTROPHY
2.1 History and disease description
2.2 The DMD gene
2.3 Mutations of the DMD gene
2.4 Dystrophin and the Dystrophin Associated Protein Complex
2.5 Dystrophin isoforms
2.6 The Dystrophin Associated Protein Complex
2.7 Animal models for DMD
2.7.1 The mdx mouse
2.7.2 The GRMD dog
2.7.3 The HFMD cat
2.8 Revertant fibers
2.9 Treatment strategies for DMD
2.9.1 Gene therapy
2.9.2 The exon skipping
2.9.3 Cell therapies
2.9.4 The pharmacological approach
3. CHAPTER: MYOSTATIN
3.1 Myostatin gene and protein structure
3.2 The myostatin knockout mouse model
3.3 Myostatin expression
3.4 The myostatin signaling pathway
3.5 Regulation of myostatin activity
3.5.1 Molecules binding myostatin
3.6 The function of myostatin
3.6.1 Myoblast cell proliferation
3.6.2 Myoblast cell differentiation
3.6.3 Muscle cell regeneration
3.6.4 The role of myostatin in adipogenesis
3.6.5 Contractile phenotype
3.6.6 Muscle metabolism
3.7 Therapeutic strategies based on myostatin blockade
3.7.1 The different approaches to induce myostatin blockade
3.7.2 Myostatin blockade as a therapy against DMD
RESULTS
1. Part 1: Role of myostatin in the regulation of muscle energetic metabolism in mouse models
1.1 Effect of the ActRIIB blockade in wildtype and mdx mice
1.2 Effect of the absence of myostatin in the Mstn-/- mouse model
2. Part 2: The role of the myostatin blockade in combination with gene therapy muscular dystrophy.
GENERAL DISCUSSION
1. Myostatin and muscle force
2. Myostatin and endurance capacity
3. Myostatin and muscle metabolism
4. Myostatin and mitochondria
5. Myostatin and vascularization
6. Myostatin and heart muscle
7. Myostatin blockade as a therapeutic strategy
BIBLIOGRAPHY
