Protein Misfolding Diseases

Protein misfolding diseases (PMDs) are a large group of >50 human disorders caused by the misfolding of specific proteins. They include serious conditions with high socio-economic impact, such as Alzheimer’s disease, systemic amyloidosis, amyotrophic lateral sclerosis, cystic fibrosis, retinitis pigmentosa and type 2 diabetes. The vast majority of PMDs remain incurable and, thus, effective therapeutics against these conditions are in enormous demand. Different PMDs are associated with different proteins (soluble or membrane-bound, globular or intrinsically disordered etc.), they affect different organs (brain, lungs, heart, eyes etc.) and they present very distinct pathologies (neurodegeneration, heart failure, blindness, carcinogenesis etc.). Yet, quite remarkably, protein misfolding has been recognized as a common molecular feature underlying all of them. This mechanistic unification constitutes a tremendous opportunity for drug discovery.

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