1. Roles of molecular chaperones in protein misfolding diseases.
- Author
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Barral JM, Broadley SA, Schaffar G, and Hartl FU
- Subjects
- Amyloid chemistry, Amyloid physiology, Chaperonin 60 genetics, Chaperonin 60 physiology, Chaperonins physiology, Cysteine Endopeptidases physiology, Cytosol physiology, Endoplasmic Reticulum physiology, Eye Proteins genetics, Eye Proteins physiology, GTP-Binding Proteins, Group II Chaperonins, HSP70 Heat-Shock Proteins physiology, HSP90 Heat-Shock Proteins physiology, Heat-Shock Proteins genetics, Heat-Shock Proteins physiology, Humans, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Models, Biological, Molecular Chaperones genetics, Multienzyme Complexes physiology, Mutation, Proteasome Endopeptidase Complex, Proteins physiology, Ubiquitins physiology, alpha-Crystallins genetics, alpha-Crystallins physiology, Disease etiology, Molecular Chaperones physiology, Protein Folding, Proteins chemistry
- Abstract
Human misfolding diseases result from the failure of proteins to reach their active state or from the accumulation of aberrantly folded proteins. The mechanisms by which molecular chaperones influence the development of these diseases is beginning to be understood. Mutations that compromise the activity of chaperones lead to several rare syndromes. In contrast, the more frequent amyloid-related neurodegenerative diseases are caused by a gain of toxic function of misfolded proteins. Toxicity in these disorders may result from an imbalance between normal chaperone capacity and production of dangerous protein species. Increased chaperone expression can suppress the neurotoxicity of these molecules, suggesting possible therapeutic strategies.
- Published
- 2004
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