ABSTRACT
When a protein is produced in the ribosome it exits into the cytoplasm and becomes in benign cases properly folded; it then begins to function. In the event of protein misfolding, disordered aggregates may form and grow in size and nally form insoluble brils, characterized by β-structure. The misfolding and aggregation are multistep processes that may occur inside or outside cells, depending on the actual protein or peptide. Often the processes are kinetically described as starting from a small template or seed, which may take a relatively long time to form, but after its formation the aggregates may grow much faster. Figure 28.1 illustrates this classical picture of amyloid formation. On the way to the larger aggregates and brils, there are medium-sized soluble entities called protobrils or oligomers. These aggregation intermediates are nowadays the most suspected species for damaging the neurons and causing neuronal dysfunction in the brain diseases. This is in contrast to an earlier concept when the most easily observable amyloid brils were the focus of attention for understanding the diseases. The brils could, in principle, even be considered as a “safe” storage place for extracellular garbage, which may, however, function as a reservoir for the soluble species.
