Protein Homeostasis Diseases: Mechanisms and Novel Therapies

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.

Provides an interdisciplinary examination of protein homeostasis disorders, with an emphasis on treatment strategies employing small natural and pharmacological ligandsOffers applied approaches in employing high throughput sequencing and screening to develop pharmacological chaperones to treat protein homeostasis diseaseGathers expertise from a range of international chapter authors who work across various biological methods and disease specific disciplines of relevance

I. Introduction of protein folding and homeostasis 1. Protein folding: how, why, and beyond 2. Protein homeostasis and disease

II. Protein folding and homeostasis at the organismal and proteomic scales 3. Caenorhabditis elegans as a model organism for protein homeostasis diseases 4. Proteome-scale studies of protein stability 5. Classifying disease-associated variants using measures of protein activity and stability

III. Protein homeostasis disturbance in disease: Genetics, mechanisms, and modulation by natural ligands 6. Protein destabilization and degradation as a mechanism for hereditary disease 7. Detection of amyloid aggregation in living systems 8. Molecular mechanisms of amyloid aggregation in human proteinopathies 9. Metals and amyloid gain-of-toxic mechanisms in neurodegenerative diseases 10. Vitamin B6-dependent enzymes and disease 11. Galactosemia: opportunities for novel therapies 12. Protein homeostasis and regulation of intracellular trafficking of G protein-coupled receptors 13. Structure-guided discovery of pharmacological chaperones targeting protein conformational and misfolding diseases 14. Virtual screening in drug discovery: a precious tool for a still-demanding challenge 15. Differential scanning fluorimetry in the screening and validation of pharmacological chaperones for soluble and membrane proteins 16. Cellular high-throughput screening 17. High-throughput screening for intrinsically disordered proteins by using biophysical methods 18. Natural and pharmacological chaperones against accelerated protein degradation: uroporphyrinogen III synthase and congenital erythropoietic porphyria