The coalescence of proteins into highly ordered aggregates is a hallmark of protein misfolding disorders (PMDs), which, when affecting the central nervous system, lead to progressive neurodegeneration. Although the chemical identity and the topology of each culprit protein are unique, the principles governing aggregation and propagation are strikingly stereotypical. It is now clear that such protein aggregates can spread from cell to cell and eventually affect entire organ systems - similarly to prion diseases. However, because most aggregates are not found to transmit between individuals, they are not infectious sensu strictiori. Therefore, they are not identical to prions and we prefer to define them as 'prionoids'. Here we review recent advances in understanding the toxicity of protein aggregation affecting the brain.