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Nat Rev Drug Discov. 2010 Mar;9(3):237-48. doi: 10.1038/nrd3050.

Protein aggregation diseases: pathogenicity and therapeutic perspectives.

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Institute of Neuropathology, University Hospital of Zürich, Schmelzbergstrasse 12, CH8091 Zürich, Switzerland.


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.

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