TY  - JOUR
AU  - Bajić, Vladan
AU  - Su, Bo
AU  - Lee, Hyoung-Gon
AU  - Kudo, Wataru
AU  - Siedlak, Sandra L.
AU  - Živković, Lada
AU  - Potparević, Biljana
AU  - Đelić, Ninoslav
AU  - Milicević, Zorana
AU  - Singh, Avneet K.
AU  - Fahmy, Lara M.
AU  - Wang, Xinglong
AU  - Smith, Mark A.
AU  - Zhu, Xiongwei
PY  - 2011
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1554
AB  - Post-mitotic neurons are typically terminally differentiated and in a quiescent status. However, in Alzheimer disease (AD), many neurons display ectopic re-expression of cell cycle-related proteins. Cyclin-dependent kinase 11 (CDK11) mRNA produces a 110-kDa protein (CDK11(p110)) throughout the cell cycle, a 58-kDa protein (CDK11(p58)) that is specifically translated from an internal ribosome entry site and expressed only in the G(2)/M phase of the cell cycle, and a 46-kDa protein (CDK11(p46)) that is considered to be apoptosis specific. CDK11 is required for sister chromatid cohesion and the completion of mitosis. In this study, we found that the expression patterns of CDK11 vary such that cytoplasmic CDK11 is increased in AD cellular processes, compared to a pronounced nuclear expression pattern in most controls. We also investigated the effect of amyloid precursor protein (APP) on CDK11 expression in vitro by using M17 cells overexpressing wild-type APP and APP Swedish mutant phenotype and found increased CDK11 expression compared to empty vector. In addition, amyloid-beta(25-35) resulted in increased CDK11 in M17 cells. These data suggest that CDK11 may play a vital role in cell cycle re-entry in AD neurons in an APP-dependent manner, thus presenting an intriguing novel function of the APP signaling pathway in AD.
PB  - BMC, LONDON
T2  - Cellular & Molecular Biology Letters
T1  - Mislocalization of CDK11/PITSLRE, a regulator of the G2/M phase of the cell cycle, in Alzheimer disease
VL  - 16
IS  - 3
SP  - 359
EP  - 372
DO  - 10.2478/s11658-011-0011-2
ER  - 

@article{
author = "Bajić, Vladan and Su, Bo and Lee, Hyoung-Gon and Kudo, Wataru and Siedlak, Sandra L. and Živković, Lada and Potparević, Biljana and Đelić, Ninoslav and Milicević, Zorana and Singh, Avneet K. and Fahmy, Lara M. and Wang, Xinglong and Smith, Mark A. and Zhu, Xiongwei",
year = "2011",
abstract = "Post-mitotic neurons are typically terminally differentiated and in a quiescent status. However, in Alzheimer disease (AD), many neurons display ectopic re-expression of cell cycle-related proteins. Cyclin-dependent kinase 11 (CDK11) mRNA produces a 110-kDa protein (CDK11(p110)) throughout the cell cycle, a 58-kDa protein (CDK11(p58)) that is specifically translated from an internal ribosome entry site and expressed only in the G(2)/M phase of the cell cycle, and a 46-kDa protein (CDK11(p46)) that is considered to be apoptosis specific. CDK11 is required for sister chromatid cohesion and the completion of mitosis. In this study, we found that the expression patterns of CDK11 vary such that cytoplasmic CDK11 is increased in AD cellular processes, compared to a pronounced nuclear expression pattern in most controls. We also investigated the effect of amyloid precursor protein (APP) on CDK11 expression in vitro by using M17 cells overexpressing wild-type APP and APP Swedish mutant phenotype and found increased CDK11 expression compared to empty vector. In addition, amyloid-beta(25-35) resulted in increased CDK11 in M17 cells. These data suggest that CDK11 may play a vital role in cell cycle re-entry in AD neurons in an APP-dependent manner, thus presenting an intriguing novel function of the APP signaling pathway in AD.",
publisher = "BMC, LONDON",
journal = "Cellular & Molecular Biology Letters",
title = "Mislocalization of CDK11/PITSLRE, a regulator of the G2/M phase of the cell cycle, in Alzheimer disease",
volume = "16",
number = "3",
pages = "359-372",
doi = "10.2478/s11658-011-0011-2"
}

Bajić, V., Su, B., Lee, H., Kudo, W., Siedlak, S. L., Živković, L., Potparević, B., Đelić, N., Milicević, Z., Singh, A. K., Fahmy, L. M., Wang, X., Smith, M. A.,& Zhu, X.. (2011). Mislocalization of CDK11/PITSLRE, a regulator of the G2/M phase of the cell cycle, in Alzheimer disease. in Cellular & Molecular Biology Letters
BMC, LONDON., 16(3), 359-372.
https://doi.org/10.2478/s11658-011-0011-2

Bajić V, Su B, Lee H, Kudo W, Siedlak SL, Živković L, Potparević B, Đelić N, Milicević Z, Singh AK, Fahmy LM, Wang X, Smith MA, Zhu X. Mislocalization of CDK11/PITSLRE, a regulator of the G2/M phase of the cell cycle, in Alzheimer disease. in Cellular & Molecular Biology Letters. 2011;16(3):359-372.
doi:10.2478/s11658-011-0011-2 .

Bajić, Vladan, Su, Bo, Lee, Hyoung-Gon, Kudo, Wataru, Siedlak, Sandra L., Živković, Lada, Potparević, Biljana, Đelić, Ninoslav, Milicević, Zorana, Singh, Avneet K., Fahmy, Lara M., Wang, Xinglong, Smith, Mark A., Zhu, Xiongwei, "Mislocalization of CDK11/PITSLRE, a regulator of the G2/M phase of the cell cycle, in Alzheimer disease" in Cellular & Molecular Biology Letters, 16, no. 3 (2011):359-372,
https://doi.org/10.2478/s11658-011-0011-2 . .

TY  - JOUR
AU  - Bonda, David J.
AU  - Bajić, Vladan
AU  - Potparević, Biljana
AU  - Casadesus, G.
AU  - Zhu, Xiongwei
AU  - Smith, Mark A.
AU  - Lee, Hyoung-Gon
PY  - 2010
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1378
AB  - The cell cycle is a highly regulated and fundamental cellular process that involves complex feedback regulation of many proteins, and any compromise to its integrity elicits dire consequences for the cell. For example, in neurodegenerative diseases such as Alzheimer disease (AD), evidence for abnormal cell cycle re-entry precedes other hallmarks of disease and as such, implicates cell cycle aberrations in the aetiology of AD. The mechanism(s) for cell cycle re-entry in AD, however, remain unclear. Current theory suggests it to be part of a combination of early events that together elicit the degenerative pathology and cognitive phenotype consistent with the disease. We propose a 'Two-Hit Hypothesis' that highlights the concerted interaction between cell cycle alterations and oxidative stress that combine to produce neurodegeneration. Here, we review the evidence implicating cell cycle mechanisms in AD and how such changes, especially in combination with oxidative stress, would lead to a cascade of events leading to disease. Based on this concept, we propose new opportunities for disease treatment.
PB  - Wiley, Hoboken
T2  - Neuropathology and Applied Neurobiology
T1  - Review: Cell cycle aberrations and neurodegeneration
VL  - 36
IS  - 2
SP  - 157
EP  - 163
DO  - 10.1111/j.1365-2990.2010.01064.x
ER  - 

@article{
author = "Bonda, David J. and Bajić, Vladan and Potparević, Biljana and Casadesus, G. and Zhu, Xiongwei and Smith, Mark A. and Lee, Hyoung-Gon",
year = "2010",
abstract = "The cell cycle is a highly regulated and fundamental cellular process that involves complex feedback regulation of many proteins, and any compromise to its integrity elicits dire consequences for the cell. For example, in neurodegenerative diseases such as Alzheimer disease (AD), evidence for abnormal cell cycle re-entry precedes other hallmarks of disease and as such, implicates cell cycle aberrations in the aetiology of AD. The mechanism(s) for cell cycle re-entry in AD, however, remain unclear. Current theory suggests it to be part of a combination of early events that together elicit the degenerative pathology and cognitive phenotype consistent with the disease. We propose a 'Two-Hit Hypothesis' that highlights the concerted interaction between cell cycle alterations and oxidative stress that combine to produce neurodegeneration. Here, we review the evidence implicating cell cycle mechanisms in AD and how such changes, especially in combination with oxidative stress, would lead to a cascade of events leading to disease. Based on this concept, we propose new opportunities for disease treatment.",
publisher = "Wiley, Hoboken",
journal = "Neuropathology and Applied Neurobiology",
title = "Review: Cell cycle aberrations and neurodegeneration",
volume = "36",
number = "2",
pages = "157-163",
doi = "10.1111/j.1365-2990.2010.01064.x"
}

Bonda, D. J., Bajić, V., Potparević, B., Casadesus, G., Zhu, X., Smith, M. A.,& Lee, H.. (2010). Review: Cell cycle aberrations and neurodegeneration. in Neuropathology and Applied Neurobiology
Wiley, Hoboken., 36(2), 157-163.
https://doi.org/10.1111/j.1365-2990.2010.01064.x

Bonda DJ, Bajić V, Potparević B, Casadesus G, Zhu X, Smith MA, Lee H. Review: Cell cycle aberrations and neurodegeneration. in Neuropathology and Applied Neurobiology. 2010;36(2):157-163.
doi:10.1111/j.1365-2990.2010.01064.x .

Bonda, David J., Bajić, Vladan, Potparević, Biljana, Casadesus, G., Zhu, Xiongwei, Smith, Mark A., Lee, Hyoung-Gon, "Review: Cell cycle aberrations and neurodegeneration" in Neuropathology and Applied Neurobiology, 36, no. 2 (2010):157-163,
https://doi.org/10.1111/j.1365-2990.2010.01064.x . .

TY  - JOUR
AU  - Bajić, Vladan
AU  - Potparević, Biljana
AU  - Živković, Lada
AU  - Bonda, David J.
AU  - Siedlak, Sandra L.
AU  - Casadesus, Gemma
AU  - Lee, Hyoung-Gon
AU  - Smith, Mark A.
PY  - 2009
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1212
AB  - Premature centromere division, or premature centromere separation (PCS), occurs when chromatid separation is dysfunctional, occurring earlier than usual during the interphase stage of mitosis. This phenomenon, seen in Robert's syndrome and various cancers, has also been documented in peripheral as well as neuronal cells of Alzheimer's disease (AD). In the latter instances, fluorescent in situ hybridization (FISH), applied to the centromere region of the X-chromosome in interphase nuclei of lymphocytes from peripheral blood in AD patients, demonstrated premature chromosomal separation before mitotic metaphase directly after completion of DNA replication in G(2) phase of the cell cycle. Furthermore, and perhaps unexpectedly given the presumptive post-mitotic status of terminally differentiated neurons, neurons in AD patients also showed significantly increased levels of PCS of the X-chromosome. Taken together with other phenomena such as cell cycle re-activation and ectopic re-expression of cyclins and cyclin dependent proteins, we propose that AD is an oncogenic phenotype leading to accelarated aging of the affected brain.
PB  - Churchill Livingstone, Edinburgh
T2  - Medical Hypotheses
T1  - The X-chromosome instability phenotype in Alzheimer's disease: A clinical sign of accelerating aging?
VL  - 73
IS  - 6
SP  - 917
EP  - 920
DO  - 10.1016/j.mehy.2009.06.046
ER  - 

@article{
author = "Bajić, Vladan and Potparević, Biljana and Živković, Lada and Bonda, David J. and Siedlak, Sandra L. and Casadesus, Gemma and Lee, Hyoung-Gon and Smith, Mark A.",
year = "2009",
abstract = "Premature centromere division, or premature centromere separation (PCS), occurs when chromatid separation is dysfunctional, occurring earlier than usual during the interphase stage of mitosis. This phenomenon, seen in Robert's syndrome and various cancers, has also been documented in peripheral as well as neuronal cells of Alzheimer's disease (AD). In the latter instances, fluorescent in situ hybridization (FISH), applied to the centromere region of the X-chromosome in interphase nuclei of lymphocytes from peripheral blood in AD patients, demonstrated premature chromosomal separation before mitotic metaphase directly after completion of DNA replication in G(2) phase of the cell cycle. Furthermore, and perhaps unexpectedly given the presumptive post-mitotic status of terminally differentiated neurons, neurons in AD patients also showed significantly increased levels of PCS of the X-chromosome. Taken together with other phenomena such as cell cycle re-activation and ectopic re-expression of cyclins and cyclin dependent proteins, we propose that AD is an oncogenic phenotype leading to accelarated aging of the affected brain.",
publisher = "Churchill Livingstone, Edinburgh",
journal = "Medical Hypotheses",
title = "The X-chromosome instability phenotype in Alzheimer's disease: A clinical sign of accelerating aging?",
volume = "73",
number = "6",
pages = "917-920",
doi = "10.1016/j.mehy.2009.06.046"
}

Bajić, V., Potparević, B., Živković, L., Bonda, D. J., Siedlak, S. L., Casadesus, G., Lee, H.,& Smith, M. A.. (2009). The X-chromosome instability phenotype in Alzheimer's disease: A clinical sign of accelerating aging?. in Medical Hypotheses
Churchill Livingstone, Edinburgh., 73(6), 917-920.
https://doi.org/10.1016/j.mehy.2009.06.046

Bajić V, Potparević B, Živković L, Bonda DJ, Siedlak SL, Casadesus G, Lee H, Smith MA. The X-chromosome instability phenotype in Alzheimer's disease: A clinical sign of accelerating aging?. in Medical Hypotheses. 2009;73(6):917-920.
doi:10.1016/j.mehy.2009.06.046 .

Bajić, Vladan, Potparević, Biljana, Živković, Lada, Bonda, David J., Siedlak, Sandra L., Casadesus, Gemma, Lee, Hyoung-Gon, Smith, Mark A., "The X-chromosome instability phenotype in Alzheimer's disease: A clinical sign of accelerating aging?" in Medical Hypotheses, 73, no. 6 (2009):917-920,
https://doi.org/10.1016/j.mehy.2009.06.046 . .