title: Implications of protein structure instability: from physiological to pathological secondary structure.
abstract: Proteins are folded during their synthesis; this process may be spontaneous or assisted. Both phenomena are carefully regulated by the "housekeeping" mechanism and molecular chaperones to avoid the appearance of misfolded proteins. Unfolding process generally occurs during physiological degradation of protein, but in some specific cases it results from genetic or environmental changes and does not correspond to metabolic needs. The main outcome of these phenomena is the appearance of nonfunctional pathologically unfolded proteins with a strong tendency to aggregation. Moreover, for some of these unfolded proteins, the agglomeration that follows initial proteins association may give rise to highly structured soluble aggregates. These aggregates have been identified as the main cause of the so-called amyloidosis or amyloid diseases, such as Alzheimer's, Parkinson's, and Creutzfeldt-Jakob diseases, and type II diabetes mellitus. Although some common mechanisms of amyloid protein aggregation have been identified, the roles of the environmental conditions inducing amyloidosis remain to be clarified. In this review, we will summarize recent studies identifying the origin of amyloid nucleation and will try to predict the therapeutic prospects that may be opened by elucidation of the amyloidosis mechanisms.
authors.affiliation: Institute of Molecular Medicine, Trinity College Dublin, Dublin 8, Ireland. nanomedicine.mephi@gmail.com
authors.forename: Alyona
authors.initials: A
authors.lastname: Sukhanova
authors.forename: Simon
authors.initials: S
authors.lastname: Poly
authors.forename: Anton
authors.initials: A
authors.lastname: Shemetov
authors.forename: Igor
authors.initials: I
authors.lastname: Bronstein
authors.forename: Igor
authors.initials: I
authors.lastname: Nabiev
mesh_terms: D058227:Amyloidogenic Proteins / Q000737:chemistry* / Q000502:physiology; D000686:Amyloidosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D007562:Creutzfeldt-Jakob Syndrome / Q000209:etiology / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000378:metabolism; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism; D017510:Protein Folding; D017433:Protein Structure, Secondary / Q000502:physiology*; D058767:Protein Unfolding; D059748:Proteolysis
chemical_list: D058227:Amyloidogenic Proteins; D018832:Molecular Chaperones