Aberrant protein interactions in amyloid disease

How protein aggregation causes cytotoxicity and disease is not yet well understood. A recent study, employing artificial beta-sheet proteins as a model, provided new insight into the mechanisms by which amyloid-like aggregation can cause far-reaching disturbances in the proteome network. Quantitative proteomics revealed that a group of metastable proteins are particularly vulnerable to sequestration by the aggregates. These proteins are generally large in size and enriched in unstructured regions, properties that are associated with a high degree of functionality as network hubs. They have key functions in transcription, translation, trafficking and cytoskeletal organization. Thus, co-aggregation of a diverse set of proteins with essential functions is likely to explain, at least in part, the multi-factorial and severe toxicity resulting from intracellular amyloidogenesis.