A direct role for large tau aggregates in neurodegeneration has been challenged by new data indicating that, in relation to degeneration of neurons, caspase activation precedes tangle formation. The findings suggest that any toxic tau moiety related to neurodegeneration is likely to be soluble rather than aggregated.
This is a preview of subscription content, access via your institution
Relevant articles
Open Access articles citing this article.
-
Exploring the significance of caspase-cleaved tau in tauopathies and as a complementary pathology to phospho-tau in Alzheimer’s disease: implications for biomarker development and therapeutic targeting
Acta Neuropathologica Communications Open Access 28 February 2024
-
Complicated Role of Post-translational Modification and Protease-Cleaved Fragments of Tau in Alzheimer’s Disease and Other Tauopathies
Molecular Neurobiology Open Access 20 December 2023
-
Co-expression of truncated and full-length tau induces severe neurotoxicity
Molecular Psychiatry Open Access 02 February 2016
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Cras, P. et al. Extracellular neurofibrillary tangles reflect neuronal loss and provide further evidence of extensive protein cross-linking in Alzheimer disease. Acta Neuropathol. 89, 291–295 (1995).
Morsch, R., Simon, W. & Coleman, P. D. Neurons may live for decades with neurofibrillary tangles. J. Neuropathol. Exp. Neurol. 58, 188–197 (1999).
de Calignon, A. et al. Caspase activation precedes and leads to tangles. Nature 464, 1201–1204 (2010).
Gamblin, T. C. et al. Caspase cleavage of tau: linking amyloid and neurofibrillary tangles in Alzheimer's disease. Proc. Natl Acad. Sci. USA 100, 10032–10037 (2003).
Berry, R. W. et al. Inhibition of tau polymerization by its carboxy-terminal caspase cleavage fragment. Biochemistry 42, 8325–8331 (2003).
de Calignon, A., Spires-Jones, T. L., Pitstick, R., Carlson, G. A. & Hyman, B. T. Tangle-bearing neurons survive despite disruption of membrane integrity in a mouse model of tauopathy. J. Neuropathol. Exp. Neurol. 68, 757–761 (2009).
Delobel, P. et al. Analysis of tau phosphorylation and truncation in a mouse model of human tauopathy. Am. J. Pathol. 172, 123–131 (2008).
Rissman, R. A. et al. Caspase-cleavage of tau is an early event in Alzheimer disease tangle pathology. J. Clin. Invest. 114, 121–130 (2004).
Lucas, J. J. et al. Decreased nuclear β-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3β conditional transgenic mice. EMBO J. 20, 27–39 (2001).
Guillozet-Bongaarts, A. L. et al. Pseudophosphorylation of tau at serine 422 inhibits caspase cleavage: in vitro evidence and implications for tangle formation in vivo. J. Neurochem. 97, 1005–1014 (2006).
Author information
Authors and Affiliations
Ethics declarations
Competing interests
The author declares no competing financial interests.
Rights and permissions
About this article
Cite this article
Avila, J. Caspases first. Nat Rev Neurol 6, 587–588 (2010). https://doi.org/10.1038/nrneurol.2010.157
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrneurol.2010.157
This article is cited by
-
Exploring the significance of caspase-cleaved tau in tauopathies and as a complementary pathology to phospho-tau in Alzheimer’s disease: implications for biomarker development and therapeutic targeting
Acta Neuropathologica Communications (2024)
-
Complicated Role of Post-translational Modification and Protease-Cleaved Fragments of Tau in Alzheimer’s Disease and Other Tauopathies
Molecular Neurobiology (2023)
-
Co-expression of truncated and full-length tau induces severe neurotoxicity
Molecular Psychiatry (2016)
