Hostname: page-component-78c5997874-dh8gc Total loading time: 0 Render date: 2024-11-08T08:08:38.090Z Has data issue: false hasContentIssue false
  • English
  • Français

Pathological implications of cell cycle re-entry in Alzheimer disease

Published online by Cambridge University Press:  29 June 2010

David J. Bonda ,
Hyun-pil Lee ,
Wataru Kudo ,
Xiongwei Zhu ,
Mark A. Smith  and
Hyoung-gon Lee
David J. Bonda
Affiliation:
Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
Hyun-pil Lee
Affiliation:
Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
Wataru Kudo
Affiliation:
Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
Xiongwei Zhu
Affiliation:
Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
Mark A. Smith*
Affiliation:
Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
Hyoung-gon Lee
Affiliation:
Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
*
*Corresponding author: Mark A. Smith, Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, Ohio 44106, USA. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

The complex neurodegeneration underlying Alzheimer disease (AD), although incompletely understood, is characterised by an aberrant re-entry into the cell cycle in neurons. Pathological evidence, in the form of cell cycle markers and regulatory proteins, suggests that cell cycle re-entry is an early event in AD, which precedes the formation of amyloid-β plaques and neurofibrillary tangles (NFTs). Although the exact mechanisms that induce and mediate these cell cycle events in AD are not clear, significant advances have been made in further understanding the pathological role of cell cycle re-entry in AD. Importantly, recent studies indicate that cell cycle re-entry is not a consequence, but rather a cause, of neurodegeneration, suggesting that targeting of cell cycle re-entry may provide an opportunity for therapeutic intervention. Moreover, multiple inducers of cell cycle re-entry and their interactions in AD have been proposed. Here, we review the most recent advances in understanding the pathological implications of cell cycle re-entry in AD.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 12 , January 2010 , e19
Copyright
Copyright © Cambridge University Press 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

References

1Smith, M.A. (1998) Alzheimer disease. International Review of Neurobiology 42, 1-54CrossRefGoogle ScholarPubMed
2Korenberg, J.R. et al. (1989) The Alzheimer amyloid precursor protein maps to human chromosome 21 bands q21.105–q21.05. Genomics 5, 124-127CrossRefGoogle Scholar
3Hellstrom-Lindahl, E., Viitanen, M. and Marutle, A. (2009) Comparison of Abeta levels in the brain of familial and sporadic Alzheimer's disease. Neurochemistry International 55, 243-252CrossRefGoogle ScholarPubMed
4Moreira, P.I. et al. (2008) Alzheimer disease and the role of free radicals in the pathogenesis of the disease. CNS and Neurological Disorders Drug Targets 7, 3-10Google ScholarPubMed
5Nunomura, A. et al. (2007) Neuronal death and survival under oxidative stress in Alzheimer and Parkinson diseases. CNS and Neurological Disorders Drug Targets 6, 411-423CrossRefGoogle ScholarPubMed
6Kontush, A. et al. (2001) Amyloid-beta is an antioxidant for lipoproteins in cerebrospinal fluid and plasma. Free Radical Biology and Medicine 30, 119-128CrossRefGoogle ScholarPubMed
7Zou, K. et al. (2002) A novel function of monomeric amyloid beta-protein serving as an antioxidant molecule against metal-induced oxidative damage. Journal of Neuroscience 22, 4833-4841CrossRefGoogle ScholarPubMed
8Morgan, D. (2009) The role of microglia in antibody-mediated clearance of amyloid-beta from the brain. CNS and Neurological Disorders Drug Targets 8, 7-15CrossRefGoogle ScholarPubMed
9Piazza, A. and Lynch, M.A. (2009) Neuroinflammatory changes increase the impact of stressors on neuronal function. Biochemical Society Transactions 37, 303-307CrossRefGoogle ScholarPubMed
10Ong, W.Y. and Farooqui, A.A. (2005) Iron, neuroinflammation, and Alzheimer's disease. Journal of Alzheimer's Disease 8, 183-200CrossRefGoogle ScholarPubMed
11Schubert, D. et al. (1989) Amyloid beta protein precursor is a mitogen. Biochemical and Biophysical Research Communications 162, 83-88CrossRefGoogle ScholarPubMed
12Milward, E.A. et al. (1992) The amyloid protein precursor of Alzheimer's disease is a mediator of the effects of nerve growth factor on neurite outgrowth. Neuron 9, 129-137CrossRefGoogle ScholarPubMed
13Copani, A. et al. (1999) Mitotic signaling by beta-amyloid causes neuronal death. FASEB Journal 13, 2225-2234CrossRefGoogle ScholarPubMed
14Iqbal, K. et al. (1984) Alzheimer paired helical filaments: bulk isolation, solubility, and protein composition. Acta Neuropathologica 62, 167-177CrossRefGoogle ScholarPubMed
15Grundke-Iqbal, I. et al. (1986) Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proceedings of the National Academy of Sciences of the United States of America 83, 4913-4917CrossRefGoogle ScholarPubMed
16Brion, J.P. (2006) Immunological demonstration of tau protein in neurofibrillary tangles of Alzheimer's disease. Journal of Alzheimer's Disease 9, 177-185CrossRefGoogle ScholarPubMed
17Brion, J.P., Octave, J.N. and Couck, A.M. (1994) Distribution of the phosphorylated microtubule-associated protein tau in developing cortical neurons. Neuroscience 63, 895-909CrossRefGoogle ScholarPubMed
18Zhu, X. et al. (2007) Alzheimer disease, the two-hit hypothesis: an update. Biochimica et Biophysica Acta 1772, 494-502CrossRefGoogle ScholarPubMed
19Nunomura, A. et al. (2000) Neuronal oxidative stress precedes amyloid-beta deposition in Down syndrome. Journal of Neuropathology and Experimental Neurology 59, 1011-1017CrossRefGoogle ScholarPubMed
20McShea, A., Wahl, A.F. and Smith, M.A. (1999) Re-entry into the cell cycle: a mechanism for neurodegeneration in Alzheimer disease. Medical Hypotheses 52, 525-527CrossRefGoogle ScholarPubMed
21Sherr, C.J. (1994) G1 phase progression: cycling on cue. Cell 79, 551-555CrossRefGoogle Scholar
22Grana, X. and Reddy, E.P. (1995) Cell cycle control in mammalian cells: role of cyclins, cyclin dependent kinases (CDKs), growth suppressor genes and cyclin-dependent kinase inhibitors (CKIs). Oncogene 11, 211-219Google ScholarPubMed
23Meikrantz, W. and Schlegel, R. (1995) Apoptosis and the cell cycle. Journal of Cellular Biochemistry 58, 160-174CrossRefGoogle ScholarPubMed
24McShea, A. et al. (1997) Abnormal expression of the cell cycle regulators P16 and CDK4 in Alzheimer's disease. American Journal of Pathology 150, 1933-1939Google ScholarPubMed
25Nagy, Z., Esiri, M.M. and Smith, A.D. (1997) Expression of cell division markers in the hippocampus in Alzheimer's disease and other neurodegenerative conditions. Acta Neuropathologica 93, 294-300CrossRefGoogle ScholarPubMed
26Smith, T.W. and Lippa, C.F. (1995) Ki-67 immunoreactivity in Alzheimer's disease and other neurodegenerative disorders. Journal of Neuropathology and Experimental Neurology 54, 297-303CrossRefGoogle ScholarPubMed
27Vincent, I., Rosado, M. and Davies, P. (1996) Mitotic mechanisms in Alzheimer's disease? Journal of Cell Biology 132, 413-425CrossRefGoogle ScholarPubMed
28Vincent, I. et al. (1997) Aberrant expression of mitotic cdc2/cyclin B1 kinase in degenerating neurons of Alzheimer's disease brain. Journal of Neuroscience 17, 3588-3598CrossRefGoogle ScholarPubMed
29Nagy, Z. et al. (1997) Cell cycle markers in the hippocampus in Alzheimer's disease. Acta Neuropathologica 94, 6-15CrossRefGoogle ScholarPubMed
30Bonda, D.J. et al. (2009) Evidence for the progression through S-phase in the ectopic cell cycle re-entry of neurons in Alzheimer disease. Aging 1, 382-388CrossRefGoogle ScholarPubMed
31Yang, Y., Geldmacher, D.S. and Herrup, K. (2001) DNA replication precedes neuronal cell death in Alzheimer's disease. Journal of Neuroscience 21, 2661-2668CrossRefGoogle ScholarPubMed
32Mosch, B. et al. (2007) Aneuploidy and DNA replication in the normal human brain and Alzheimer's disease. Journal of Neuroscience 27, 6859-6867CrossRefGoogle ScholarPubMed
33Zhu, X. et al. (2008) Neuronal binucleation in Alzheimer disease hippocampus. Neuropathology and Applied Neurobiology 34, 457-465CrossRefGoogle ScholarPubMed
34Spremo-Potparevic, B. et al. (2008) Premature centromere division of the X chromosome in neurons in Alzheimer's disease. Journal of Neurochemistry 106, 2218-2223CrossRefGoogle ScholarPubMed
35Gartner, U., Holzer, M. and Arendt, T. (1999) Elevated expression of p21ras is an early event in Alzheimer's disease and precedes neurofibrillary degeneration. Neuroscience 91, 1-5CrossRefGoogle ScholarPubMed
36McShea, A. et al. (2007) Neuronal cell cycle re-entry mediates Alzheimer disease-type changes. Biochimica et Biophysica Acta 1772, 467-472CrossRefGoogle ScholarPubMed
37Zhu, X. et al. (2004) Neuronal cell cycle re-entry: a doomed journey in Alzheimer disease? In Frontiers in Neurodegenerative Disorders and Aging: Fundamental Aspects, Clinical Perspectives and New Insights Özben, T. and Chevion, M., eds), pp. 200-206, IOS Press, AmsterdamGoogle Scholar
38Zhu, X. et al. (2001) Differential activation of neuronal ERK, JNK/SAPK and p38 in Alzheimer disease: the 'two hit' hypothesis. Mechanisms of Ageing and Development 123, 39-46CrossRefGoogle ScholarPubMed
39Zhu, X. et al. (2003) Distribution, levels, and activation of MEK1 in Alzheimer's disease. Journal of Neurochemistry 86, 136-142CrossRefGoogle ScholarPubMed
40Manzano, S. et al. (2009) [Genetics and Alzheimer's disease.]. Neurologia 24, 83-89Google Scholar
41Prat, M.I. et al. (2002) Presenilin 1 overexpressions in Chinese hamster ovary (CHO) cells decreases the phosphorylation of retinoblastoma protein: relevance for neurodegeneration. Neuroscience Letters 326, 9-12CrossRefGoogle ScholarPubMed
42Varvel, N.H. et al. (2008) Abeta oligomers induce neuronal cell cycle events in Alzheimer's disease. Journal of Neuroscience 28, 10786-10793CrossRefGoogle ScholarPubMed
43Neve, R.L. and McPhie, D.L. (2007) Dysfunction of amyloid precursor protein signaling in neurons leads to DNA synthesis and apoptosis. Biochimica et Biophysica Acta 1772, 430-437CrossRefGoogle ScholarPubMed
44Zhu, X., Raina, A.K. and Smith, M.A. (1999) Cell cycle events in neurons. Proliferation or death? American Journal of Pathology 155, 327-329CrossRefGoogle ScholarPubMed
45Li, J. et al. (1997) Alzheimer presenilins in the nuclear membrane, interphase kinetochores, and centrosomes suggest a role in chromosome segregation. Cell 90, 917-927CrossRefGoogle ScholarPubMed
46Janicki, S.M., Stabler, S.M. and Monteiro, M.J. (2000) Familial Alzheimer's disease presenilin-1 mutants potentiate cell cycle arrest. Neurobiology of Aging 21, 829-836CrossRefGoogle ScholarPubMed
47Janicki, S.M. and Monteiro, M.J. (1999) Presenilin overexpression arrests cells in the G1 phase of the cell cycle. Arrest potentiated by the Alzheimer's disease PS2(N141I)mutant. American Journal of Pathology 155, 135-144CrossRefGoogle ScholarPubMed
48Soriano, S. et al. (2001) Presenilin 1 negatively regulates beta-catenin/T cell factor/lymphoid enhancer factor-1 signaling independently of beta-amyloid precursor protein and notch processing. Journal of Cell Biology 152, 785-794CrossRefGoogle ScholarPubMed
49Ogawa, O. et al. (2003) Ectopic localization of phosphorylated histone H3 in Alzheimer's disease: a mitotic catastrophe? Acta Neuropathologica 105, 524-528CrossRefGoogle ScholarPubMed
50Zhu, X. et al. (2006) Apoptosis in Alzheimer disease: a mathematical improbability. Current Alzheimer Research 3, 393-396CrossRefGoogle ScholarPubMed
51Perry, G. et al. (1998) Apoptosis and Alzheimer's disease. Science 282, 1268-1269CrossRefGoogle ScholarPubMed
52Feddersen, R.M. et al. (1992) Disrupted cerebellar cortical development and progressive degeneration of Purkinje cells in SV40 T antigen transgenic mice. Neuron 9, 955-966CrossRefGoogle ScholarPubMed
53Park, K.H. et al. (2007) Conditional neuronal simian virus 40 T antigen expression induces Alzheimer-like tau and amyloid pathology in mice. Journal of Neuroscience 27, 2969-2978CrossRefGoogle ScholarPubMed
54al-Ubaidi, M.R. et al. (1992) Photoreceptor degeneration induced by the expression of simian virus 40 large tumor antigen in the retina of transgenic mice. Proceedings of the National Academy of Sciences of the United States of America 89, 1194-1198CrossRefGoogle ScholarPubMed
55Giovanni, A. et al. (1999) Involvement of cell cycle elements, cyclin-dependent kinases, pRb, and E2F x DP, in B-amyloid-induced neuronal death. Journal of Biological Chemistry 274, 19011-19016CrossRefGoogle ScholarPubMed
56Park, D.S. et al. (2000) Cell cycle regulators in neuronal death evoked by excitotoxic stress: implications for neurodegeneration and its treatment. Neurobiology of Aging 21, 771-781CrossRefGoogle ScholarPubMed
57Lee, H.G. et al. (2009) The neuronal expression of MYC causes a neurodegenerative phenotype in a novel transgenic mouse. American Journal of Pathology 174, 891-897CrossRefGoogle Scholar
58Dang, C.V., Le, A. and Gao, P. (2009) MYC-induced cancer cell energy metabolism and therapeutic opportunities. Clinical Cancer Research 15, 6479-6483CrossRefGoogle ScholarPubMed
59Ferrer, I. et al. (2001) Phosphorylated c-MYC expression in Alzheimer disease, Pick's disease, progressive supranuclear palsy and corticobasal degeneration. Neuropathology and Applied Neurobiology 27, 343-351CrossRefGoogle ScholarPubMed
60Zhu, X. et al. (2004) Alzheimer's disease: the two-hit hypothesis. Lancet Neurology 3, 219-226CrossRefGoogle ScholarPubMed
61Yang, Y. et al. (2006) Ectopic cell cycle events link human Alzheimer's disease and amyloid precursor protein transgenic mouse models. Journal of Neuroscience 26, 775-784CrossRefGoogle ScholarPubMed
62Zhu, X. et al. (2005) Oxidative imbalance in Alzheimer's disease. Molecular Neurobiology 31, 205-217CrossRefGoogle ScholarPubMed
63Ogawa, O. et al. (2002) Mitochondrial abnormalities and oxidative imbalance in neurodegenerative disease. Science of Aging Knowledge Environment 2002, pe16CrossRefGoogle ScholarPubMed
64Morsch, R., Simon, W. and Coleman, P.D. (1999) Neurons may live for decades with neurofibrillary tangles. Journal of Neuropathology and Experimental Neurology 58, 188-197CrossRefGoogle ScholarPubMed
65Varvel, N.H. et al. (2009) NSAIDs prevent, but do not reverse, neuronal cell cycle reentry in a mouse model of Alzheimer disease. Journal of Clinical Investigation 119, 3692-3702CrossRefGoogle ScholarPubMed
66Woods, J., Snape, M. and Smith, M.A. (2007) The cell cycle hypothesis of Alzheimer's disease: Suggestions for drug development. Biochimica et Biophysica Acta 1772, 503-508CrossRefGoogle ScholarPubMed
67Breuer, B. and Anderson, R. (2000) The relationship of tamoxifen with dementia, depression, and dependence in activities of daily living in elderly nursing home residents. Women and Health 31, 71-85CrossRefGoogle ScholarPubMed
68Previll, L.A. et al. (2007) Increased expression of p130 in Alzheimer disease. Neurochemical Research 32, 639-644CrossRefGoogle ScholarPubMed
69Thakur, A. et al. (2008) Retinoblastoma protein phosphorylation at multiple sites is associated with neurofibrillary pathology in Alzheimer disease. International Journal of Clinical and Experimental Pathology 1, 134-146Google ScholarPubMed
70Zhu, X. et al. (2004) Elevated expression of a regulator of the G2/M phase of the cell cycle, neuronal CIP-1-associated regulator of cyclin B, in Alzheimer's disease. Journal of Neuroscience Research 75, 698-703CrossRefGoogle ScholarPubMed
71Evans, T.A. et al. (2007) BRCA1 may modulate neuronal cell cycle re-entry in Alzheimer disease. International Journal of Medical Sciences 4, 140-145CrossRefGoogle ScholarPubMed
72Kubiak, J.Z. and Smith, M.A. (2010) Ubiquitin/proteasome system in mitotic and mitotic-like regulation during brain development and pathology. In The Ubiquitin Proteasome System in the Central Nervous System: From Physiology to Pathology (2008 update) Di Napoli, M. and Wojcik, C., eds.), pp. 113-130, Nova Science Publishers, NY, USAGoogle Scholar
Zhu, X. et al. (2007) Alzheimer disease, the two-hit hypothesis: an update. Biochimica et Biophysica Acta 1772, 494-502CrossRefGoogle ScholarPubMed
Nagy, Z., Esiri, M.M. and Smith, A.D. (1997) Expression of cell division markers in the hippocampus in Alzheimer's disease and other neurodegenerative conditions. Acta Neuropathologica 93, 294-300CrossRefGoogle ScholarPubMed
Woods, J., Snape, M. and Smith, M.A. (2007) The cell cycle hypothesis of Alzheimer's disease: Suggestions for drug development. Biochimica et Biophysica Acta 1772, 503-508CrossRefGoogle ScholarPubMed
Zhu, X. et al. (2007) Alzheimer disease, the two-hit hypothesis: an update. Biochimica et Biophysica Acta 1772, 494-502CrossRefGoogle ScholarPubMed
Nagy, Z., Esiri, M.M. and Smith, A.D. (1997) Expression of cell division markers in the hippocampus in Alzheimer's disease and other neurodegenerative conditions. Acta Neuropathologica 93, 294-300CrossRefGoogle ScholarPubMed
Woods, J., Snape, M. and Smith, M.A. (2007) The cell cycle hypothesis of Alzheimer's disease: Suggestions for drug development. Biochimica et Biophysica Acta 1772, 503-508CrossRefGoogle ScholarPubMed
Zhu, X. et al. (2007) Alzheimer disease, the two-hit hypothesis: an update. Biochimica et Biophysica Acta 1772, 494-502CrossRefGoogle ScholarPubMed
Nagy, Z., Esiri, M.M. and Smith, A.D. (1997) Expression of cell division markers in the hippocampus in Alzheimer's disease and other neurodegenerative conditions. Acta Neuropathologica 93, 294-300CrossRefGoogle ScholarPubMed
Woods, J., Snape, M. and Smith, M.A. (2007) The cell cycle hypothesis of Alzheimer's disease: Suggestions for drug development. Biochimica et Biophysica Acta 1772, 503-508CrossRefGoogle ScholarPubMed