Predicting the aggregation propensity of prion sequences.

The presence of prions can result in debilitating and neurodegenerative diseases in mammals and protein-based genetic elements in fungi. Prions are defined as a subclass of amyloids in which the self-aggregation process becomes self-perpetuating and infectious. Like all amyloids, prions polymerize into fibres with a common core formed of β-sheet structures oriented perpendicular to the fibril axes which form a structure known as a cross-β structure. The intermolecular β-sheet propensity, a characteristic of the amyloid pattern, as well as other key parameters of amyloid fibril formation can be predicted. Mathematical algorithms have been proposed to predict both amyloid and prion propensities. However, it has been shown that the presence of amyloid-prone regions in a polypeptide sequence could be insufficient for amyloid formation. It has also often been stated that the formation of amyloid fibrils does not imply that these are prions. Despite these limitations, in silico prediction of amyloid and prion propensities should help detect potential new prion sequences in mammals. In addition, the determination of amyloid-prone regions in prion sequences could be very useful in understanding the effect of sporadic mutations and polymorphisms as well as in the search for therapeutic targets.