It is currently unclear which forms of the protein tau contribute to Alzheimer disease (AD) pathology, but Δtau314, which is produced following caspase 2-mediated tau cleavage, is elevated in the brains of cognitively impaired mice and humans with AD. Here, in vitro expression of a mutant form of tau that was resistant to caspase 2 cleavage reduced tau accumulation in dendritic spines and tau-induced synaptic dysfunction. Moreover, knockdown of caspase 2 expression in the rTg4510 mouse tauopathy model improved long-term memory in mice with existing deficits; thus, caspase 2 inhibition might have therapeutic potential in human tauopathies.
References
Zhao, X. et al. Caspase-2 cleavage of tau reversibly impairs memory. Nat. Med. http://dx.doi.org/10.1038/nm.4199 (2016)
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Lewis, S. Resisting the chop. Nat Rev Neurosci 17, 739 (2016). https://doi.org/10.1038/nrn.2016.153
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DOI: https://doi.org/10.1038/nrn.2016.153