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Publication : Cell-cycle reentry and cell death in transgenic mice expressing nonmutant human tau isoforms.

First Author  Andorfer C Year  2005
Journal  J Neurosci Volume  25
Issue  22 Pages  5446-54
PubMed ID  15930395 Mgi Jnum  J:98717
Mgi Id  MGI:3579730 Doi  10.1523/JNEUROSCI.4637-04.2005
Citation  Andorfer C, et al. (2005) Cell-cycle reentry and cell death in transgenic mice expressing nonmutant human tau isoforms. J Neurosci 25(22):5446-54
abstractText  Mutations in the microtubule-associated protein tau gene have been linked to neurofibrillary tangle (NFT) formation in several neurodegenerative diseases known as tauopathies; however, no tau mutations occur in Alzheimer's disease, although this disease is also characterized by NFT formation and cell death. Importantly, the mechanism of tau-mediated neuronal death remains elusive. Aged mice expressing nonmutant human tau in the absence of mouse tau (htau mice) developed NFTs and extensive cell death. The mechanism of neuron death was investigated in htau mice, and surprisingly, the presence of tau filaments did not correlate directly with death within individual cells, suggesting that cell death can occur independently of NFT formation. Our observations show that the mechanism of neurodegeneration involved reexpression of cell-cycle proteins and DNA synthesis, indicating that nonmutant tau pathology and neurodegeneration may be linked via abnormal, incomplete cell-cycle reentry.
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