Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

AMYLOID DISEASES

Enlightening amyloid fibrils linked to type 2 diabetes and cross-interactions with Aβ

Nature Structural & Molecular Biology volume 27, pages 1006–1008 (2020)Cite this article

Subjects

Three recent studies report cryo-EM structures of amyloid fibrils of islet amyloid polypeptide (IAPP), which are linked to type 2 diabetes (T2D) pathogenesis. The results shed light on the structural basis of IAPP fibril formation, reveal remarkable similarities between IAPP and Aβ fibrils and will inform the design of anti-amyloid drugs in T2D and Alzheimer’s disease (AD).

Pancreatic islet amyloid deposits, initially termed ‘hyaline material’, are linked to the pathogenesis of type 2 diabetes (T2D)1,2. In fact, self-assembly of the major amyloid component, islet amyloid polypeptide (IAPP), plays a key role in pancreatic β-cell degeneration in T2D2. Interestingly, increasing evidence suggests that IAPP aggregation may also be linked to Alzheimer’s disease (AD)3,4,5,6,7. However, the molecular and structural basis of IAPP self-assembly and how it could be linked to the two diseases are not yet sufficiently understood. Now, 120 years after the discovery of the ‘hyaline material’, we finally gain near-atomic level insight into IAPP amyloid fibrils, provided by cryo-EM structures from Röder et al.8, Cao et al.9 and Gallardo et al.10. These studies also shed light on the fibril structure of S20G-IAPP, a mutant linked to hereditary early-onset T2D; uncover remarkable structural similarities between IAPP and Aβ fibrils, suggesting possible cross-seeding interfaces; and offer an IAPP-based structural template for the design of new anti-amyloid molecules.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Cryo-EM structures of IAPP fibrils and implications for T2D and AD pathogenesis.

References

  1. Opie, E. L. J. Exp. Med. 5, 397–428 (1901).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Westermark, P., Andersson, A. & Westermark, G. T. Physiol. Rev. 91, 795–826 (2011).

    Article  CAS  PubMed  Google Scholar 

  3. Jackson, K. et al. Ann. Neurol. 74, 517–526 (2013).

    Article  CAS  PubMed  Google Scholar 

  4. Moreno-Gonzalez, I. et al. Mol. Psychiatry 22, 1327–1334 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. OʼNuallain, B., Williams, A. D., Westermark, P. & Wetzel, R. J. Biol. Chem. 279, 17490–17499 (2004).

    Article  PubMed  Google Scholar 

  6. Oskarsson, M. E. et al. Am. J. Pathol. 185, 834–846 (2015).

    Article  CAS  PubMed  Google Scholar 

  7. Yan, L.-M., Velkova, A., Tatarek-Nossol, M., Andreetto, E. & Kapurniotu, A. Angew. Chem. Int. Ed. Engl. 46, 1246–1252 (2007).

    Article  CAS  PubMed  Google Scholar 

  8. Röder, C. et al. Nat. Struct. Mol. Biol. 27, 660–667 (2020).

    Article  PubMed  Google Scholar 

  9. Cao, Q., Boyer, D. R., Sawaya, M. R., Ge, P. & Eisenberg, D. S. Nat. Struct. Mol. Biol. 27, 653–659 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gallardo, R. et al. Nat. Struct. Mol. Biol. https://doi.org/10.1038/s41594-020-0496-3 (2020).

  11. Westermark, P., Wernstedt, C., Wilander, E. & Sletten, K. Biochem. Biophys. Res. Commun. 140, 827–831 (1986).

    Article  CAS  PubMed  Google Scholar 

  12. Andreetto, E. et al. Angew. Chem. Int. Ed. Engl. 49, 3081–3085 (2010).

    Article  CAS  PubMed  Google Scholar 

  13. Yan, L.-M., Velkova, A. & Kapurniotu, A. Curr. Pharm. Des. 20, 1182–1191 (2014).

    Article  CAS  PubMed  Google Scholar 

  14. Akter, K. et al. Br. J. Clin. Pharmacol. 71, 365–376 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Luca, S., Yau, W.-M., Leapman, R. & Tycko, R. Biochemistry 46, 13505–13522 (2007).

    Article  CAS  PubMed  Google Scholar 

  16. Wiltzius, J. J. W. et al. Protein Sci. 17, 1467–1474 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Weirich, F. et al. PLoS ONE 11, e0161243 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Kajava, A. V., Aebi, U. & Steven, A. C. J. Mol. Biol. 348, 247–252 (2005).

    Article  CAS  PubMed  Google Scholar 

  19. Westermark, P., Engström, U., Johnson, K. H., Westermark, G. T. & Betsholz, C. Proc. Natl Acad. Sci. USA 87, 5036–5040 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Tenidis, K. et al. J. Mol. Biol. 295, 1055–1071 (2000).

    Article  CAS  PubMed  Google Scholar 

  21. Buchanan, L. E. et al. Proc. Natl Acad. Sci. USA 110, 19285–19290 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ashburn, T. T., Auger, M. & Lansbury, P. T. Jr. J. Am. Chem. Soc. 114, 790–791 (1992).

    Article  CAS  Google Scholar 

  23. Yan, L.-M., Tatarek-Nossol, M., Velkova, A., Kazantzis, A. & Kapurniotu, A. Proc. Natl Acad. Sci. USA 103, 2046–2051 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Armiento, V., Spanopoulou, A. & Kapurniotu, A. Angew. Chem. Int. Ed. Engl. 59, 3372–3384 (2020).

    Article  CAS  PubMed  Google Scholar 

  25. Petkova, A. T. et al. Proc. Natl Acad. Sci. USA 99, 16742–16747 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Luo, J., Wärmländer, S. K. T. S., Gräslund, A. & Abrahams, J. P. J. Biol. Chem. 291, 16485–16493 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Horvath, I. & Wittung-Stafshede, P. Proc. Natl Acad. Sci. USA 113, 12473–12477 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Gremer, L. et al. Science 358, 116–119 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Financial support by the Deutsche Forschungsgemeinschaft (SFB 1035; B06) is gratefully acknowledged.

Author information

Authors and Affiliations

  1. Division of Peptide Biochemistry, TUM School of Life Sciences, Technical University of Munich (TUM), Freising, Germany

    Aphrodite Kapurniotu

Authors
  1. Aphrodite Kapurniotu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Aphrodite Kapurniotu.

Ethics declarations

Competing interests

The author is a coinventor on patents and patent applications for designed peptides as inhibitors of IAPP and Aβ amyloid formation and their use in the treatment of T2D and AD.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kapurniotu, A. Enlightening amyloid fibrils linked to type 2 diabetes and cross-interactions with Aβ. Nat Struct Mol Biol 27, 1006–1008 (2020). https://doi.org/10.1038/s41594-020-00523-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41594-020-00523-z

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing