Figure 1 Schematic representation of the possible mechanism of formation of amyloid fibrils by a globular protein. After synthesis on the ribosome, the protein is assumed to fold in the endoplasmic reticulum (ER), aided by molecular chaperones that deter aggregation of incompletely folded species. The correctly folded protein is secreted from the cell and functions normally in its extracellular environment. Under certain conditions the protein unfolds, at least partially, and becomes prone to aggregation. This can result in the formation of fibrils and other aggregates that accumulate in tissue. It is likely that small aggregates, as well as the highly organized fibrils and plaques, can give rise to pathological conditions in at least some cases. N, I and U refer to native, partially folded (intermediate) and unfolded states of the protein, respectively. QC refers to the quality control mechanism that prevents incompletely folded proteins being secreted from the endoplasmic reticulum35.