Protein Homeostasis Diseases: Mechanisms and Novel Therapies offers an interdisciplinary examination of the fundamental aspects, biochemistry and molecular biology of protein homeostasis disease, including the use of natural and pharmacological small molecules to treat common and rare protein homeostasis disorders. Contributions from international experts discuss the biochemical and genetic components of protein homeostasis disorders, the mechanisms by which genetic variants may cause loss-of-function and gain-of-toxic-function, and how natural ligands can restore protein function and homeostasis in genetic diseases. Applied chapters provide guidance on employing high throughput sequencing and screening methodologies to develop pharmacological chaperones and repurpose approved drugs to treat protein homeostasis disorders.
1. Section I: Introduction of protein folding and homeostasis - p. xx 2. Chapter 1: Protein folding: how, why, and beyond - p. xx 3. Chapter 2: Protein homeostasis and disease - p. 22 4. Section II: Protein folding and homeostasis at the organismal and proteomic scales - p. 37 5. Chapter 3: Caenorhabditis elegans as a model organism for protein homeostasis diseases - p. 37 6. Chapter 4: Proteome-scale studies of protein stability - p. 69 7. Chapter 5: Classifying disease-associated variants using measures of protein activity and stability - p. 90 8. Section III: Protein homeostasis disturbance in disease: genetics, mechanisms, and modulation by natural ligands - p. 107 9. Chapter 6: Protein destabilization and degradation as a mechanism for hereditary disease - p. 107 10. Chapter 7: Detection of amyloid aggregation in living systems - p. 125 11. Chapter 8: Molecular mechanisms of amyloid aggregation in human proteinopathies - p. 152 12. Chapter 9: Metals and amyloid gain-of-toxic mechanisms in neurodegenerative diseases - p. 179 13. Chapter 10: Vitamin B6-dependent enzymes and disease - p. 195 14. Chapter 11: Galactosemia: opportunities for novel therapies - p. 220 15. Chapter 12: Protein homeostasis and regulation of intracellular trafficking of G protein-coupled receptors - p. 245 16. Section IV: Identification of novel small molecules to correct human protein diseases - p. 277 17. Chapter 13: Structure-guided discovery of pharmacological chaperones targeting protein conformational and misfolding diseases - p. 277 18. Chapter 14: Virtual screening in drug discovery: a precious tool for a still-demanding challenge - p. 308 19. Chapter 15: Differential scanning fluorimetry in the screening and validation of pharmacological chaperones for soluble and membrane proteins - p. 327 20. Chapter 16: Cellular high-throughput screening - p. 341 21. Chapter 17: High-throughput screening for intrinsically disordered proteins by using biophysical methods - p. 358 22. Chapter 18: Natural and pharmacological chaperones against accelerated protein degradation: uroporphyrinogen III synthase and congenital erythropoietic porphyria - p. 387 23. Index - p. 413
Protein Homeostasis Diseases: Mechanisms and Novel Therapies offers an interdisciplinary examination of the fundamental aspects, biochemistry and molecular biology of protein homeostasis disease, including the use of natural and pharmacological small molecules to treat common and rare protein homeostasis disorders. Contributions from international experts discuss the biochemical and genetic components of protein homeostasis disorders, the mechanisms by which genetic variants may cause loss-of-function and gain-of-toxic-function, and how natural ligands can restore protein function and homeostasis in genetic diseases. Applied chapters provide guidance on employing high throughput sequencing and screening methodologies to develop pharmacological chaperones and repurpose approved drugs to treat protein homeostasis disorders.
1. Section I: Introduction of protein folding and homeostasis - p. xx 2. Chapter 1: Protein folding: how, why, and beyond - p. xx 3. Chapter 2: Protein homeostasis and disease - p. 22 4. Section II: Protein folding and homeostasis at the organismal and proteomic scales - p. 37 5. Chapter 3: Caenorhabditis elegans as a model organism for protein homeostasis diseases - p. 37 6. Chapter 4: Proteome-scale studies of protein stability - p. 69 7. Chapter 5: Classifying disease-associated variants using measures of protein activity and stability - p. 90 8. Section III: Protein homeostasis disturbance in disease: genetics, mechanisms, and modulation by natural ligands - p. 107 9. Chapter 6: Protein destabilization and degradation as a mechanism for hereditary disease - p. 107 10. Chapter 7: Detection of amyloid aggregation in living systems - p. 125 11. Chapter 8: Molecular mechanisms of amyloid aggregation in human proteinopathies - p. 152 12. Chapter 9: Metals and amyloid gain-of-toxic mechanisms in neurodegenerative diseases - p. 179 13. Chapter 10: Vitamin B6-dependent enzymes and disease - p. 195 14. Chapter 11: Galactosemia: opportunities for novel therapies - p. 220 15. Chapter 12: Protein homeostasis and regulation of intracellular trafficking of G protein-coupled receptors - p. 245 16. Section IV: Identification of novel small molecules to correct human protein diseases - p. 277 17. Chapter 13: Structure-guided discovery of pharmacological chaperones targeting protein conformational and misfolding diseases - p. 277 18. Chapter 14: Virtual screening in drug discovery: a precious tool for a still-demanding challenge - p. 308 19. Chapter 15: Differential scanning fluorimetry in the screening and validation of pharmacological chaperones for soluble and membrane proteins - p. 327 20. Chapter 16: Cellular high-throughput screening - p. 341 21. Chapter 17: High-throughput screening for intrinsically disordered proteins by using biophysical methods - p. 358 22. Chapter 18: Natural and pharmacological chaperones against accelerated protein degradation: uroporphyrinogen III synthase and congenital erythropoietic porphyria - p. 387 23. Index - p. 413
