Protein aggregation diseases pathogenicity and therapeutic perspectives英文文献.pdfVIP

R E V I E W S Protein aggregation diseases: pathogenicity and therapeutic perspectives Adriano Aguzzi and Tracy O’Connor Abstract | A growing number of diseases seem to be associated with inappropriate deposition of protein aggregates. Some of these diseases — such as Alzheimer’s disease and systemic amyloidoses — have been recognized for a long time. However, it is now clear that ordered aggregation of pathogenic proteins does not only occur in the extracellular space, but in the cytoplasm and nucleus as well, indicating that many other diseases may also qualify as amyloidoses. The common structural and pathogenic features of these diverse protein aggregation diseases is only now being fully understood, and may provide novel opportunities for overarching therapeutic approaches such as depleting the monomeric precursor protein, inhibiting aggregation, enhancing aggregate clearance or blocking common aggregation-induced cellular toxicity pathways. Inappropriate aggregation of proteins is normally systemic amyloidoses in which deposits may occur in prevented by complex cellular quality control mecha- any part of the body, such as AL amyloidosis due to the nisms. However, under certain circumstances, an unusual accumulation of immunoglobulin light chai