title: Roles of molecular chaperones in protein misfolding diseases.
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.
authors.affiliation: Department of Cellular Biochemistry, Max-Planck-Institut für Biochemie, Am Klopferspitz 18a, D-82152 Martinsried, Germany.
authors.forename: José M
authors.initials: JM
authors.lastname: Barral
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Broadley
authors.forename: Gregor
authors.initials: G
authors.lastname: Schaffar
authors.forename: F Ulrich
authors.initials: FU
authors.lastname: Hartl
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000502:physiology; D018834:Chaperonin 60 / Q000235:genetics / Q000502:physiology; D018833:Chaperonins / Q000502:physiology; D003546:Cysteine Endopeptidases / Q000502:physiology; D003600:Cytosol / Q000502:physiology; D004194:Disease / Q000209:etiology*; D004721:Endoplasmic Reticulum / Q000502:physiology; D005136:Eye Proteins / Q000235:genetics / Q000502:physiology; D019204:GTP-Binding Proteins; D056385:Group II Chaperonins; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology; D018841:HSP90 Heat-Shock Proteins / Q000502:physiology; D006360:Heat-Shock Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008954:Models, Biological; D018832:Molecular Chaperones / Q000235:genetics / Q000502:physiology*; D009097:Multienzyme Complexes / Q000502:physiology; D009154:Mutation; D046988:Proteasome Endopeptidase Complex; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000502:physiology; D014452:Ubiquitins / Q000502:physiology; D038201:alpha-Crystallins / Q000235:genetics / Q000502:physiology
chemical_list: D000682:Amyloid; D018834:Chaperonin 60; D005136:Eye Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; C414726:MKKS protein, human; D008565:Membrane Proteins; D018832:Molecular Chaperones; D009097:Multienzyme Complexes; D011506:Proteins; C072178:RP2 protein, human; C404403:SACS protein, human; C469270:TBCE protein, human; D014452:Ubiquitins; D038201:alpha-Crystallins; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D018833:Chaperonins; D019204:GTP-Binding Proteins; D056385:Group II Chaperonins