 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
The Journal of Neuroscience, June 1, 2005, 25(22):5446-5454; doi:10.1523/JNEUROSCI.4637-04.2005
Previous Article | Next Article
Neurobiology of Disease
Cell-Cycle Reentry and Cell Death in Transgenic Mice Expressing Nonmutant Human Tau Isoforms
Cathy Andorfer,1 Christopher M. Acker,2 Yvonne Kress,2 Patrick R. Hof,3 Karen Duff,4 andPeter Davies1,2 Departments of 1Neuroscience and 2Pathology, Albert Einstein College of Medicine, Bronx, New York 10461, 3Kastor Neurobiology of Aging Laboratories and Fishberg Research Center for Neurobiology, Department of Geriatrics and Adult Development, and Department of Ophthalmology, Mount Sinai School of Medicine, New York, New York 10029, and 4Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York 10962
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.
Key words: cell cycle; neurofibrillary tangle; cell death; transgenic; nonmutant tau; neurodegeneration
Received Nov 11, 2004; revised April 14, 2005; accepted April 26, 2005.
This article has been cited by other articles:
M. I. Kester, A. E. van der Vlies, M. A. Blankenstein, Y.A.L. Pijnenburg, E. J. van Elk, P. Scheltens, and W. M. van der Flier
CSF biomarkers predict rate of cognitive decline in Alzheimer disease
Neurology, October 27, 2009; 73(17): 1353 - 1358.
[Abstract] [Full Text] [PDF]
M. Polydoro, C. M. Acker, K. Duff, P. E. Castillo, and P. Davies
Age-Dependent Impairment of Cognitive and Synaptic Function in the htau Mouse Model of Tau Pathology
J. Neurosci., August 26, 2009; 29(34): 10741 - 10749.
[Abstract] [Full Text] [PDF]
J. J.M. Hoozemans, E. S. van Haastert, D. A.T. Nijholt, A. J.M. Rozemuller, P. Eikelenboom, and W. Scheper
The Unfolded Protein Response Is Activated in Pretangle Neurons in Alzheimer's Disease Hippocampus
Am. J. Pathol., April 1, 2009; 174(4): 1241 - 1251.
[Abstract] [Full Text] [PDF]
W. Noble, C. Garwood, J. Stephenson, A. M. Kinsey, D. P. Hanger, and B. H. Anderton
Minocycline reduces the development of abnormal tau species in models of Alzheimer's disease
FASEB J, March 1, 2009; 23(3): 739 - 750.
[Abstract] [Full Text] [PDF]
V. Kallhoff-Munoz, L. Hu, X. Chen, R. G. Pautler, and H. Zheng
Genetic Dissection of {gamma}-Secretase-Dependent and-Independent Functions of Presenilin in Regulating Neuronal Cell Cycle and Cell Death
J. Neurosci., October 29, 2008; 28(44): 11421 - 11431.
[Abstract] [Full Text] [PDF]
T. L. Spires-Jones, A. de Calignon, T. Matsui, C. Zehr, R. Pitstick, H.-Y. Wu, J. D. Osetek, P. B. Jones, B. J. Bacskai, M. B. Feany, et al.
In Vivo Imaging Reveals Dissociation between Caspase Activation and Acute Neuronal Death in Tangle-Bearing Neurons
J. Neurosci., January 23, 2008; 28(4): 862 - 867.
[Abstract] [Full Text] [PDF]
A. A. Asuni, A. Boutajangout, D. Quartermain, and E. M. Sigurdsson
Immunotherapy Targeting Pathological Tau Conformers in a Tangle Mouse Model Reduces Brain Pathology with Associated Functional Improvements
J. Neurosci., August 22, 2007; 27(34): 9115 - 9129.
[Abstract] [Full Text] [PDF]
Y. P. Wang, J. Biernat, M. Pickhardt, E. Mandelkow, and E.-M. Mandelkow
Stepwise proteolysis liberates tau fragments that nucleate the Alzheimer-like aggregation of full-length tau in a neuronal cell model
PNAS, June 12, 2007; 104(24): 10252 - 10257.
[Abstract] [Full Text] [PDF]
B. Bandyopadhyay, G. Li, H. Yin, and J. Kuret
Tau Aggregation and Toxicity in a Cell Culture Model of Tauopathy
J. Biol. Chem., June 1, 2007; 282(22): 16454 - 16464.
[Abstract] [Full Text] [PDF]
Z. Berger, H. Roder, A. Hanna, A. Carlson, V. Rangachari, M. Yue, Z. Wszolek, K. Ashe, J. Knight, D. Dickson, et al.
Accumulation of Pathological Tau Species and Memory Loss in a Conditional Model of Tauopathy
J. Neurosci., April 4, 2007; 27(14): 3650 - 3662.
[Abstract] [Full Text] [PDF]
H.-L. Li, H.-H. Wang, S.-J. Liu, Y.-Q. Deng, Y.-J. Zhang, Q. Tian, X.-C. Wang, X.-Q. Chen, Y. Yang, J.-Y. Zhang, et al.
Phosphorylation of tau antagonizes apoptosis by stabilizing beta-catenin, a mechanism involved in Alzheimer's neurodegeneration
PNAS, February 27, 2007; 104(9): 3591 - 3596.
[Abstract] [Full Text] [PDF]
H.-W. Klafki, M. Staufenbiel, J. Kornhuber, and J. Wiltfang
Therapeutic approaches to Alzheimer's disease
Brain, November 1, 2006; 129(11): 2840 - 2855.
[Abstract] [Full Text] [PDF]
K. Schindowski, A. Bretteville, K. Leroy, S. Begard, J.-P. Brion, M. Hamdane, and L. Buee
Alzheimer's Disease-Like Tau Neuropathology Leads to Memory Deficits and Loss of Functional Synapses in a Novel Mutated Tau Transgenic Mouse without Any Motor Deficits
Am. J. Pathol., August 1, 2006; 169(2): 599 - 616.
[Abstract] [Full Text] [PDF]
S. Le Corre, H. W. Klafki, N. Plesnila, G. Hubinger, A. Obermeier, H. Sahagun, B. Monse, P. Seneci, J. Lewis, J. Eriksen, et al.
An inhibitor of tau hyperphosphorylation prevents severe motor impairments in tau transgenic mice
PNAS, June 20, 2006; 103(25): 9673 - 9678.
[Abstract] [Full Text] [PDF]
A. d. C. Alonso, B. Li, I. Grundke-Iqbal, and K. Iqbal
Polymerization of hyperphosphorylated tau into filaments eliminates its inhibitory activity
PNAS, June 6, 2006; 103(23): 8864 - 8869.
[Abstract] [Full Text] [PDF]
T. L. Spires, J. D. Orne, K. SantaCruz, R. Pitstick, G. A. Carlson, K. H. Ashe, and B. T. Hyman
Region-specific Dissociation of Neuronal Loss and Neurofibrillary Pathology in a Mouse Model of Tauopathy
Am. J. Pathol., May 1, 2006; 168(5): 1598 - 1607.
[Abstract] [Full Text] [PDF]
K. Boekhoorn, D. Terwel, B. Biemans, P. Borghgraef, O. Wiegert, G. J. A. Ramakers, K. de Vos, H. Krugers, T. Tomiyama, H. Mori, et al.
Improved long-term potentiation and memory in young tau-P301L transgenic mice before onset of hyperphosphorylation and tauopathy.
J. Neurosci., March 29, 2006; 26(13): 3514 - 3523.
[Abstract] [Full Text] [PDF]
A. Nunomura, R. J. Castellani, H.-g. Lee, P. I. Moreira, X. Zhu, G. Perry, and M. A. Smith
Neuropathology in Alzheimer's disease: awaking from a hundred-year-old dream.
Sci. Aging Knowl. Environ., March 22, 2006; 2006(8): pe10 - pe10.
[Abstract] [Full Text]
P. Delobel, I. Lavenir, B. Ghetti, M. Holzer, and M. Goedert
Cell-Cycle Markers in a Transgenic Mouse Model of Human Tauopathy: Increased Levels of Cyclin-Dependent Kinase Inhibitors p21Cip1 and p27Kip1
Am. J. Pathol., March 1, 2006; 168(3): 878 - 887.
[Abstract] [Full Text] [PDF]
G. Amadoro, M. T. Ciotti, M. Costanzi, V. Cestari, P. Calissano, and N. Canu
From the Cover: NMDA receptor mediates tau-induced neurotoxicity by calpain and ERK/MAPK activation
PNAS, February 21, 2006; 103(8): 2892 - 2897.
[Abstract] [Full Text] [PDF]
Y. Yang, N. H. Varvel, B. T. Lamb, and K. Herrup
Ectopic Cell Cycle Events Link Human Alzheimer's Disease and Amyloid Precursor Protein Transgenic Mouse Models
J. Neurosci., January 18, 2006; 26(3): 775 - 784.
[Abstract] [Full Text] [PDF]
M. Ramsden, L. Kotilinek, C. Forster, J. Paulson, E. McGowan, K. SantaCruz, A. Guimaraes, M. Yue, J. Lewis, G. Carlson, et al.
Age-Dependent Neurofibrillary Tangle Formation, Neuron Loss, and Memory Impairment in a Mouse Model of Human Tauopathy (P301L)
J. Neurosci., November 16, 2005; 25(46): 10637 - 10647.
[Abstract] [Full Text] [PDF]
Papers of Note
Sci. Aging Knowl. Environ., June 8, 2005; 2005(23): nw23 - nw23.
[Full Text]
|
|
|
|
 |
|