title: Amyloid polymorphism: structural basis and neurobiological relevance.
abstract: Our understanding of the molecular structures of amyloid fibrils that are associated with neurodegenerative diseases, of mechanisms by which disease-associated peptides and proteins aggregate into fibrils, and of structural properties of aggregation intermediates has advanced considerably in recent years. Detailed molecular structural models for certain fibrils and aggregation intermediates are now available. It is now well established that amyloid fibrils are generally polymorphic at the molecular level, with a given peptide or protein being capable of forming a variety of distinct, self-propagating fibril structures. Recent results from structural studies and from studies involving cell cultures, transgenic animals, and human tissue provide initial evidence that molecular structural variations in amyloid fibrils and related aggregates may correlate with or even produce variations in disease development. This article reviews our current knowledge of the structural and mechanistic aspects of amyloid formation, as well as current evidence for the biological relevance of structural variations.
authors.affiliation: Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520, USA. Electronic address: robertty@mail.nih.gov.
authors.forename: Robert
authors.initials: R
authors.lastname: Tycko
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D006801:Humans; D008958:Models, Molecular; D009446:Neurobiology; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D000682:Amyloid