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Asparagine endopeptidase cleaves tau and promotes neurodegeneration


Truncation of tau contributes to the formation of neurofibrillary tangles in Alzheimer's disease. A new study finds a direct role for a lysosomal cysteine protease, asparagine endopeptidase, in cleaving tau into neurotoxic fragments.

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Figure 1: Neurofibrillary tangles composed of aggregated tau contribute to neurodegeneration in AD.


  1. Arriagada, P.V., Growdon, J.H., Hedley-Whyte, E.T. & Hyman, B.T. Neurology 42, 631–639 (1992).

    Article  CAS  Google Scholar 

  2. Ballatore, C., Lee, V.M. & Trojanowski, J.Q. Nat. Rev. Neurosci. 8, 663–672 (2007).

    Article  CAS  Google Scholar 

  3. Avila, J., Lucas, J.J., Perez, M. & Hernandez, F. Physiol. Rev. 84, 361–384 (2004).

    Article  CAS  Google Scholar 

  4. Mandelkow, E.M. & Mandelkow, E. Cold Spring Harb. Perspect. Med. 2, a006247 (2012).

    Article  Google Scholar 

  5. Binder, L.I., Guillozet-Bongaarts, A.L., Garcia-Sierra, F. & Berry, R.W. Biochim. Biophys. Acta 1739, 216–223 (2005).

    Article  CAS  Google Scholar 

  6. Wang, Y., Garg, S., Mandelkow, E.M. & Mandelkow, E. Biochem. Soc. Trans. 38, 955–961 (2010).

    Article  CAS  Google Scholar 

  7. Zhang, Z. et al. Nat. Med. 20, 1254–1262 (2014). 10.1038/nm.3700

    Article  CAS  Google Scholar 

  8. Liu, Z. et al. Mol. Cell 29, 665–678 (2008).

    Article  CAS  Google Scholar 

  9. Herskowitz, J.H. et al. Proteomics 12, 2455–2463 (2012).

    Article  CAS  Google Scholar 

  10. Basurto-Islas, G., Grundke-Iqbal, I., Tung, Y.C., Liu, F. & Iqbal, K. J. Biol. Chem. 288, 17495–17507 (2013).

    Article  CAS  Google Scholar 

  11. Rapoport, M., Dawson, H.N., Binder, L.I., Vitek, M.P. & Ferreira, A. Proc. Natl. Acad. Sci. USA 99, 6364–6369 (2002).

    Article  CAS  Google Scholar 

  12. Park, S.Y. & Ferreira, A. J. Neurosci. 25, 5365–5375 (2005).

    Article  CAS  Google Scholar 

  13. Kayed, R. et al. Science 300, 486–489 (2003).

    Article  CAS  Google Scholar 

  14. Clavaguera, F. et al. Brain Pathol. 23, 342–349 (2013).

    Article  CAS  Google Scholar 

  15. Nakamura, Y. et al. Neurosci. Lett. 130, 195–198 (1991).

    Article  CAS  Google Scholar 

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Correspondence to Hanna Rosenmann.

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Rosenmann, H. Asparagine endopeptidase cleaves tau and promotes neurodegeneration. Nat Med 20, 1236–1238 (2014).

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