Resumen de Amyloid: a multifaceted player in human health and disease
J. Johansson, L. Olson, J. Andersson, G. Johansson, B. Winblad
Amyloid is the main constituent of protein deposits associated with certain human diseases, some of which pose major medical and socio-economic challenges. Alzheimer's disease and type II diabetes mellitus are perhaps the most well-known examples of amyloid-associated human diseases. Amyloid is also related to several functional protein assemblies, mainly in bacteria and yeast but also in arthropods and mammals. Moreover, amyloid structures have recently been found to play important roles in infectious diseases, although in opposite ways in different settings: amyloid-like nanonets trap bacteria in the gut, whereas HIV and other viruses can use binding to amyloid fibrils in order to enhance their infectivity. Amyloid is a unique and highly stable protein fold. Its properties have led to a strong interest in the possible use of amyloid-like structures made from naturally occurring proteins and peptides, or simplified designed versions thereof, for the development of novel biomaterials for regenerative medicine and other applications. The formation of insoluble amyloid fibrils from soluble proteins is a self-templated, nucleation-dependent reaction. In the case of the prion protein, this process can be transferred between individuals of the same species and also, with some barriers, between individuals of different species. The basis for this transmissibility of the prion protein is now beginning to be understood at a molecular level. It is alarming that amyloid composed of one specific protein can cross-seed the formation of amyloid by another protein and that amyloid is present in the food we eat [1]. However, there are also reasons for optimism; it is becoming increasingly clear that molecular chaperones act in different ways to maintain proteostasis and that amyloid formation, like protein folding in general, is regulated in several ways. The underlying mechanisms are promising targets for the treatment of amyloid diseases and are currently under intense investigation.
In this issue of the Journal of Internal Medicine, four review articles cover in depth four salient aspects of amyloid: the structural biology of amyloid and how its formation is modulated by molecular chaperones is reviewed by Landreh et al. [2], Bergman et al. [3] discuss the involvement of amyloid in infectious diseases, the transmissibility of amyloid is reviewed by Tjernberg et al. [4] and current trends in the treatment of amyloid diseases are considered by Ankarcrona et al. [5]. The four reviews provide summaries of presentations at a recent Nobel minisymposium in the series Frontiers in Medicine held at Karolinska Institutet, Sweden. The aim of the symposium was to highlight the immediate medical relevance of amyloid in human health and disease and to bridge the recent progress in understanding amyloid formation from preclinical studies and clinical results from treating amyloid disorders.
