title: Mechanisms of protein-folding diseases at a glance.
abstract: For a protein to function appropriately, it must first achieve its proper conformation and location within the crowded environment inside the cell. Multiple chaperone systems are required to fold proteins correctly. In addition, degradation pathways participate by destroying improperly folded proteins. The intricacy of this multisystem process provides many opportunities for error. Furthermore, mutations cause misfolded, nonfunctional forms of proteins to accumulate. As a result, many pathological conditions are fundamentally rooted in the protein-folding problem that all cells must solve to maintain their function and integrity. Here, to illustrate the breadth of this phenomenon, we describe five examples of protein-misfolding events that can lead to disease: improper degradation, mislocalization, dominant-negative mutations, structural alterations that establish novel toxic functions, and amyloid accumulation. In each case, we will highlight current therapeutic options for battling such diseases.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
authors.forename: Julie S
authors.initials: JS
authors.lastname: Valastyan
authors.forename: Susan
authors.initials: S
authors.lastname: Lindquist
mesh_terms: D000682:Amyloid / Q000378:metabolism; D003550:Cystic Fibrosis / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D055808:Drug Discovery; D005776:Gaucher Disease / Q000503:physiopathology; D005799:Genes, Dominant; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000503:physiopathology; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D057165:Proteostasis Deficiencies / Q000503:physiopathology*
chemical_list: D000682:Amyloid; D018832:Molecular Chaperones; D019005:Cystic Fibrosis Transmembrane Conductance Regulator
keywords: Disease; Misfolding; Protein; Yeast