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.
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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).
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Avila, J. Caspases first. Nat Rev Neurol 6, 587–588 (2010). https://doi.org/10.1038/nrneurol.2010.157
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DOI: https://doi.org/10.1038/nrneurol.2010.157
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