The amyloid state and its association with protein misfolding diseases

Key Points The phenomenon of amyloid formation is associated with protein misfolding disorders, including Alzheimer's disease, Parkinson's disease and type II diabetes. The amyloid state is a 'generic state' of proteins and its study can provide great insight into the nature of functional structures and into that of disease-related assemblies. A multitude of quality control, or 'housekeeping', mechanisms exist in living organisms to prevent the conversion of normally soluble proteins into the aberrant amyloid state and to maintain protein homeostasis. The failure of these quality control mechanisms can give rise to 'protein metastasis', the uncontrolled conversion of these molecules into aberrant self-propagating assemblies that ultimately lead to a cascade of cytotoxic processes. Our increasing ability to monitor and characterize the molecular structures and formation mechanisms of the protein species that are involved in amyloid formation is suggesting novel strategies to treat or prevent protein misfolding disorders. Ultimately, the results of this field of research will result in great changes in the way we are able to manage modern lifestyles and maintain healthy ageing. Protein aggregation and amyloid deposition are associated with a wide range of medical disorders, including Alzheimer's disease and type II diabetes. Studies into the amyloid state are revealing fundamental principles that underlie the maintenance of protein homeostasis, and the origins of aberrant protein behaviour and disease. The phenomenon of protein aggregation and amyloid formation has become the subject of rapidly increasing research activities across a wide range of scientific disciplines. Such activities have been stimulated by the association of amyloid deposition with a range of debilitating medical disorders, from Alzheimer's disease to type II diabetes, many of which are major threats to human health and welfare in the modern world. It has become clear, however, that the ability to form the amyloid state is more general than previously imagined, and that its study can provide unique insights into the nature of the functional forms of peptides and proteins, as well as understanding the means by which protein homeostasis can be maintained and protein metastasis avoided.