The DOI matches its Crossref record; 71 of the 71 references it cites were found in a registry or an index.
Tau Cleavage and Dephosphorylation in Cerebellar Granule Neurons Undergoing Apoptosis
Open accessAbstract
Cerebellar granule cells undergo apoptosis in culture after deprivation of potassium and serum. During this process we found that tau, a neuronal microtubule-associated protein that plays a key role in the maintenance of neuronal architecture, and the pathology of which correlates with intellectual decline in Alzheimer’s disease, is cleaved. The final product of this cleavage is a soluble dephosphorylated tau fragment of 17 kDa that is unable to associate with microtubules and accumulates in the perikarya of dying cells. The appearance of this 17 kDa fragment is inhibited by both caspase and calpain inhibitors, suggesting that tau is an in vivo substrate for both of these proteases during apoptosis. Tau cleavage is correlated with disruption of the microtubule network, and experiments with colchicine and taxol show that this is likely to be a cause and not a consequence of tau cleavage. These data indicate that tau cleavage and change in phosphorylation are important early factors in the failure of the microtubule network that occurs during neuronal apoptosis. Furthermore, this study introduces new insights into the mechanism(s) that generate the truncated forms of tau present in Alzheimer’s disease.
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“Indeed, calpain A has been shown to cleave tau and is reported to be responsible for producing a 17 kDa fragment that may be a highly toxic tau derivative (211,212).”
From Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation (2011) · cites this paper as [212]
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Cites
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Research works printed but not linked: 2
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- 10.1128/MCB.9.4.1381 · DOI
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Apoptosis: controlled demolition at the cellular level
Taylor, R. C., Cullen, S. P., & Martin, S. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2312 · Cited by 2,708
Roles of tau protein in health and disease
Guo, T., Noble, W., & Hanger, D. P. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1707-9 · Cited by 1,003
Many cuts to ruin: a comprehensive update of caspase substrates
Fischer, U., Jänicke, R. U., & Schulze‐Osthoff, K. (2003) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401160 · Cited by 1,025
Degradation of misfolded proteins in neurodegenerative diseases: Therapeutic targets and strategies
Ciechanover, A., & Kwon, Y. T. (2015) · Experimental & Molecular Medicine · doi:10.1038/emm.2014.117 · Cited by 898
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Metadata
- Authors
- Canu, N., Dus, L., Barbato, C., Ciotti, M. T., Brancolini, C., Rinaldi, A. M., Novak, M., Cattaneo, A., Bradbury, A., & Calissano, P.
- Affiliations
- University of Rome Tor Vergata (IT)
- Institute of Neurobiology and Molecular Medicine (IT)
- AREA Science Park (IT)
- Scuola Internazionale Superiore di Studi Avanzati (IT)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1998-09-15
- Volume
- 18
- Issue
- 18
- Pages
- 7061-7074
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6793249
- OpenAlex
- W2122437043
- Cited by
- 232
- References
- 71
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 1 · 2022: 4 · 2021: 3 · 2020: 6 · 2019: 6 · 2018: 13 · 2017: 7 · 2016: 3 · 2015: 7 · 2014: 13 · 2013: 9 · 2012: 6
- FWCI
- 8.40
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion, other-oa)
- Institutional Research Information System (University of Udine) (submittedVersion)
- Scuola Normale Superiore di Pisa (submittedVersion)
- Funders
- Consiglio Nazionale delle Ricerche
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- tau protein, tau cleavage, tau dephosphorylation, cerebellar granule cells, neuronal apoptosis, caspases, calpain, microtubule-associated proteins, Alzheimer's disease
- MeSH terms
- Alzheimer Disease, Animals, Antineoplastic Agents, Phytogenic, Calpain, Cerebellum, Colchicine, Cysteine Endopeptidases, Cytoskeleton, Enzyme Precursors, Microtubules, Neurons, Oligopeptides, Peptide Fragments, Phosphorylation, Solubility, Cysteine Proteinase Inhibitors, tau Proteins, Rats, Wistar, Apoptosis, Paclitaxel, Caspases, Rats, Caspase 3
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