The Concept of Protein Mosaics: Physiological Role and Relevance for Prion Disease

The tendency of the proteins to aggregate (i.e., their so-called Lego property) is viewed as a necessary feature of proteins to build up molecular networks, which are the informational substrate that allows integrative actions of cells and hence of tissues. Thus, the concept of physiological protein mosaics is discussed not only as the basis for the formation of structural elements of the cell and of the extra-cellular matrix, but also as the main component of molecular networks. Against this background, the hypothesis is introduced that prion-like properties of some proteins have a possible physiological meaning for the formation of physiological protein mosaics and hence of complex molecular networks. Protein misfolding and the Lego property can favour the formation of unwanted protein aggregates. On this basis, the concept of pathological mosaics is introduced as the most frequent consequence of alterations in the three dimensional structures of proteins, thus representing a feature characterising the conformational protein diseases. It is postulated that pathological protein mosaics affect the structure and function of the global molecular network enmeshing the whole central nervous system leading to neurodegenerative disease, the most clear cut example being Prion disease.