The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.
Tau accumulation induces synaptic impairment and memory deficit by calcineurin-mediated inactivation of nuclear CaMKIV/CREB signaling
Open accessAbstract
Intracellular accumulation of wild-type tau is a hallmark of sporadic Alzheimer’s disease (AD), but the molecular mechanisms underlying tau-induced synapse impairment and memory deficit are poorly understood. Here we found that overexpression of human wild-type full-length tau (termed hTau) induced memory deficits with impairments of synaptic plasticity. Both in vivo and in vitro data demonstrated that hTau accumulation caused remarkable dephosphorylation of cAMP response element binding protein (CREB) in the nuclear fraction. Simultaneously, the calcium-dependent protein phosphatase calcineurin (CaN) was up-regulated, whereas the calcium/calmodulin-dependent protein kinase IV (CaMKIV) was suppressed. Further studies revealed that CaN activation could dephosphorylate CREB and CaMKIV, and the effect of CaN on CREB dephosphorylation was independent of CaMKIV inhibition. Finally, inhibition of CaN attenuated the hTau-induced CREB dephosphorylation with improved synapse and memory functions. Together, these data indicate that the hTau accumulation impairs synapse and memory by CaN-mediated suppression of nuclear CaMKIV/CREB signaling. Our findings not only reveal new mechanisms underlying the hTau-induced synaptic toxicity, but also provide potential targets for rescuing tauopathies.
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Tzioras, M., McGeachan, R. I., Durrant, C. S., & Spires-Jones, T. L. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-022-00749-z · Cited by 504
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Synaptic Impairment in Alzheimer’s Disease: A Dysregulated Symphony
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Synaptic dysfunction in Alzheimer's disease: Mechanisms and therapeutic strategies
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Metadata
- Authors
- Yin, Y., Gao, D., Wang, Y., Wang, Z.-H., Wang, X., Ye, J., Wu, D., Fang, L., Pi, G., Yang, Y., Wang, X.-C., Lu, C., Ye, K., & Wang, J.-Z.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2016-06-13
- Volume
- 113
- Issue
- 26
- Pages
- E3773-81
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2429713509
- Cited by
- 174
- References
- 19
- FWCI
- 11.18
- Type
- journal article
- Language
- en
- Open access
- green
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- Yin, Y., Gao, D., Wang, Y., Wang, Z.-H., Wang, X., Ye, J., Wu, D., Fang, L., Pi, G., Yang, Y., Wang, X.-C., Lu, C., Ye, K., & Wang, J.-Z. (2016). Tau accumulation induces synaptic impairment and memory deficit by calcineurin-mediated inactivation of nuclear CaMKIV/CREB signaling. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1604519113
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