Amyloids go genomic: insights regarding the sequence determinants of prion formation from genome-wide studies.

Protein misfolding is the primary cause of several systemic and neurodegenerative diseases and a major challenge in the development of protein-based therapeutics, Figure 1 top. In misfolding diseases such as cystic fibrosis and a1-antitrypsin deficiency, degradation and/or mistrafficking of specific proteins causes loss of protein function. A second class of misfolding disease includes systemic amyloidoses, type II diabetes, Alzheimer’s disease, and Parkinson’s disease. These are caused by gains of toxic function resulting from the aggregation of specific misfolded proteins into highly ordered structures, termed amyloid fibrils, Figure 1. Amyloid-like protein aggregates that act as infectious agents by replicat-