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Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases

Author

Listed:
  • Monica Bucciantini

    (Universitá degli Studi di Firenze)

  • Elisa Giannoni

    (Universitá degli Studi di Firenze)

  • Fabrizio Chiti

    (Universitá degli Studi di Firenze
    University of Cambridge)

  • Fabiana Baroni

    (Universitá degli Studi di Firenze)

  • Lucia Formigli

    (Universitá degli Studi di Firenze)

  • Jesús Zurdo

    (University of Cambridge)

  • Niccolò Taddei

    (Universitá degli Studi di Firenze)

  • Giampietro Ramponi

    (Universitá degli Studi di Firenze)

  • Christopher M. Dobson

    (University of Cambridge)

  • Massimo Stefani

    (Universitá degli Studi di Firenze)

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.

Suggested Citation

  • Monica Bucciantini & Elisa Giannoni & Fabrizio Chiti & Fabiana Baroni & Lucia Formigli & Jesús Zurdo & Niccolò Taddei & Giampietro Ramponi & Christopher M. Dobson & Massimo Stefani, 2002. "Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases," Nature, Nature, vol. 416(6880), pages 507-511, April.
    • Handle: RePEc:nat:nature:v:416:y:2002:i:6880:d:10.1038_416507a
    DOI: 10.1038/416507a
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    Citations

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    Cited by:

    1. Qi Wang & Joshua L Johnson & Nathalie YR Agar & Jeffrey N Agar, 2008. "Protein Aggregation and Protein Instability Govern Familial Amyotrophic Lateral Sclerosis Patient Survival," PLOS Biology, Public Library of Science, vol. 6(7), pages 1-19, July.
    2. Mookyung Cheon & Iksoo Chang & Sandipan Mohanty & Leila M Luheshi & Christopher M Dobson & Michele Vendruscolo & Giorgio Favrin, 2007. "Structural Reorganisation and Potential Toxicity of Oligomeric Species Formed during the Assembly of Amyloid Fibrils," PLOS Computational Biology, Public Library of Science, vol. 3(9), pages 1-12, September.
    3. Etienne Maisonneuve & Adrien Ducret & Pierre Khoueiry & Sabrina Lignon & Sonia Longhi & Emmanuel Talla & Sam Dukan, 2009. "Rules Governing Selective Protein Carbonylation," PLOS ONE, Public Library of Science, vol. 4(10), pages 1-12, October.
    4. Noah S Bieler & Tuomas P J Knowles & Daan Frenkel & Robert Vácha, 2012. "Connecting Macroscopic Observables and Microscopic Assembly Events in Amyloid Formation Using Coarse Grained Simulations," PLOS Computational Biology, Public Library of Science, vol. 8(10), pages 1-10, October.
    5. Victor Banerjee & Rajiv K Kar & Aritreyee Datta & Krupakar Parthasarathi & Subhrangsu Chatterjee & Kali P Das & Anirban Bhunia, 2013. "Use of a Small Peptide Fragment as an Inhibitor of Insulin Fibrillation Process: A Study by High and Low Resolution Spectroscopy," PLOS ONE, Public Library of Science, vol. 8(8), pages 1-15, August.
    6. Aaron M Streets & Yannick Sourigues & Ron R Kopito & Ronald Melki & Stephen R Quake, 2013. "Simultaneous Measurement of Amyloid Fibril Formation by Dynamic Light Scattering and Fluorescence Reveals Complex Aggregation Kinetics," PLOS ONE, Public Library of Science, vol. 8(1), pages 1-10, January.
    7. Abdul Rouf Mir, 2017. "Scanning Electron Microscopic Analysis of Glycated Histone H2B," Current Trends in Biomedical Engineering & Biosciences, Juniper Publishers Inc., vol. 4(2), pages 12-14, May.
    8. Bente Vestergaard & Minna Groenning & Manfred Roessle & Jette S Kastrup & Marco van de Weert & James M Flink & Sven Frokjaer & Michael Gajhede & Dmitri I Svergun, 2007. "A Helical Structural Nucleus Is the Primary Elongating Unit of Insulin Amyloid Fibrils," PLOS Biology, Public Library of Science, vol. 5(5), pages 1-9, May.

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