Abstract
A range of human degenerative conditions, including Alzheimer's disease, light-chain amyloidosis and the spongiform encephalopathies, is associated with the deposition in tissue of proteinaceous aggregates known as amyloid fibrils or plaques. It has been shown previously that fibrillar aggregates that are closely similar to those associated with clinical amyloidoses can be formed in vitro from proteins not connected with these diseases, including the SH3 domain from bovine phosphatidyl-inositol-3′-kinase and the amino-terminal domain of the Escherichia coli HypF protein. Here we show that species formed early in the aggregation of these non-disease-associated proteins can be inherently highly cytotoxic. This finding provides added evidence that avoidance of protein aggregation is crucial for the preservation of biological function and suggests common features in the origins of this family of protein deposition diseases.
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Acknowledgements
The work was supported by grants from the Italian MIUR (PRIN “Folding e Misfolding di Proteine) and the Italian Telethon Foundation. The research of C.M.D. is supported in part by a Programme Grant from the Wellcome Trust. F.C. is supported by a fellowship from the Italian Telethon Foundation.
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Bucciantini, M., Giannoni, E., Chiti, F. et al. Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases. Nature 416, 507–511 (2002). https://doi.org/10.1038/416507a
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DOI: https://doi.org/10.1038/416507a
