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  - Živković, Lada
AU  - Potparević, Biljana
AU  - Plećaš-Solarović, Bosiljka
AU  - Đelić, Ninoslav
AU  - Ocić, Gordana
AU  - Smiljković, Predrag
AU  - Siedlak, Sandra L.
AU  - Smith, Mark A.
AU  - Bajić, Vladan
PY  - 2010
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1370
AB  - Chromosomal alterations are a feature of both aging and Alzheimer's disease (AD). This study examined if premature centromere division (PCD), a chromosomal instability indicator increased in AD, is correlated with aging or, instead, represents a de novo chromosomal alteration due to accelerating aging in AD. PCD in peripheral blood lymphocytes was determined in sporadic AD patients and gender and age-matched unaffected controls. Metaphase nuclei were analyzed for chromosomes showing PCD, X chromosomes with PCD (PCD,X), and acrocentric chromosomes showing PCD. AD patients, regardless of age, demonstrated increased PCD on any chromosome and PCD on acrocentric chromosomes in both genders, whereas an increase in frequency of PCD,X was expressed only in women. This cytogenetic analysis suggests that PCD is a feature of AD, rather than an epiphenomenon of chronological aging, and may be useful as a physiological biomarker that can be used for disease diagnosis.
PB  - Oxford Univ Press Inc, Cary
T2  - Journals of Gerontology Series A: Biological Sciences and Medical Sciences
T1  - Premature Centromere Division of Metaphase Chromosomes in Peripheral Blood Lymphocytes of Alzheimer's Disease Patients: Relation to Gender and Age
VL  - 65
IS  - 12
SP  - 1269
EP  - 1274
DO  - 10.1093/gerona/glq148
ER  - 

@article{
author = "Živković, Lada and Potparević, Biljana and Plećaš-Solarović, Bosiljka and Đelić, Ninoslav and Ocić, Gordana and Smiljković, Predrag and Siedlak, Sandra L. and Smith, Mark A. and Bajić, Vladan",
year = "2010",
abstract = "Chromosomal alterations are a feature of both aging and Alzheimer's disease (AD). This study examined if premature centromere division (PCD), a chromosomal instability indicator increased in AD, is correlated with aging or, instead, represents a de novo chromosomal alteration due to accelerating aging in AD. PCD in peripheral blood lymphocytes was determined in sporadic AD patients and gender and age-matched unaffected controls. Metaphase nuclei were analyzed for chromosomes showing PCD, X chromosomes with PCD (PCD,X), and acrocentric chromosomes showing PCD. AD patients, regardless of age, demonstrated increased PCD on any chromosome and PCD on acrocentric chromosomes in both genders, whereas an increase in frequency of PCD,X was expressed only in women. This cytogenetic analysis suggests that PCD is a feature of AD, rather than an epiphenomenon of chronological aging, and may be useful as a physiological biomarker that can be used for disease diagnosis.",
publisher = "Oxford Univ Press Inc, Cary",
journal = "Journals of Gerontology Series A: Biological Sciences and Medical Sciences",
title = "Premature Centromere Division of Metaphase Chromosomes in Peripheral Blood Lymphocytes of Alzheimer's Disease Patients: Relation to Gender and Age",
volume = "65",
number = "12",
pages = "1269-1274",
doi = "10.1093/gerona/glq148"
}

Živković, L., Potparević, B., Plećaš-Solarović, B., Đelić, N., Ocić, G., Smiljković, P., Siedlak, S. L., Smith, M. A.,& Bajić, V.. (2010). Premature Centromere Division of Metaphase Chromosomes in Peripheral Blood Lymphocytes of Alzheimer's Disease Patients: Relation to Gender and Age. in Journals of Gerontology Series A: Biological Sciences and Medical Sciences
Oxford Univ Press Inc, Cary., 65(12), 1269-1274.
https://doi.org/10.1093/gerona/glq148

Živković L, Potparević B, Plećaš-Solarović B, Đelić N, Ocić G, Smiljković P, Siedlak SL, Smith MA, Bajić V. Premature Centromere Division of Metaphase Chromosomes in Peripheral Blood Lymphocytes of Alzheimer's Disease Patients: Relation to Gender and Age. in Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 2010;65(12):1269-1274.
doi:10.1093/gerona/glq148 .

Živković, Lada, Potparević, Biljana, Plećaš-Solarović, Bosiljka, Đelić, Ninoslav, Ocić, Gordana, Smiljković, Predrag, Siedlak, Sandra L., Smith, Mark A., Bajić, Vladan, "Premature Centromere Division of Metaphase Chromosomes in Peripheral Blood Lymphocytes of Alzheimer's Disease Patients: Relation to Gender and Age" in Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 65, no. 12 (2010):1269-1274,
https://doi.org/10.1093/gerona/glq148 . .

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 . .

TY  - JOUR
AU  - Potparević, Biljana
AU  - Živković, Lada
AU  - Đelić, Ninoslav
AU  - Plećaš-Solarović, Bosiljka
AU  - Smith, Mark A.
AU  - Bajić, Vladan
PY  - 2008
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1114
AB  - Premature centromere division (PCD) represents a loss of control over the sequential separation and segregation of chromosome centromeres. Although first described in aging women, PCD on the X chromosome (PCD,X) is markedly elevated in peripheral blood lymphocytes of individuals suffering from Alzheimer disease (AD). The present study evaluated PCD,X, using a fluorescent in situ hybridization method, in interphase nuclei of frontal cerebral cortex neurons from sporadic AD patients and age-matched controls. The average frequency of PCD,X in AD patients (8.60 +/- 1.20%) was almost three times higher (p  lt  0.01) than in the control group (2.96 +/- 1.20). However, consistent with previous studies, no mitotic cells were found in neurons in either AD or control brain, suggesting an intrinsic inability of post-mitotic neurons to divide. In view of the fact that it has been well-documented that neurons in AD can re-enter into the cell division cycle, the findings presented here of increased PCD advance the hypothesis that deregulation of the cell cycle may contribute to neuronal degeneration and subsequent cognitive deficits in AD.
PB  - Wiley-Blackwell, Malden
T2  - Journal of Neurochemistry
T1  - Premature centromere division of the X chromosome in neurons in Alzheimer's disease
VL  - 106
IS  - 5
SP  - 2218
EP  - 2223
DO  - 10.1111/j.1471-4159.2008.05555.x
ER  - 

@article{
author = "Potparević, Biljana and Živković, Lada and Đelić, Ninoslav and Plećaš-Solarović, Bosiljka and Smith, Mark A. and Bajić, Vladan",
year = "2008",
abstract = "Premature centromere division (PCD) represents a loss of control over the sequential separation and segregation of chromosome centromeres. Although first described in aging women, PCD on the X chromosome (PCD,X) is markedly elevated in peripheral blood lymphocytes of individuals suffering from Alzheimer disease (AD). The present study evaluated PCD,X, using a fluorescent in situ hybridization method, in interphase nuclei of frontal cerebral cortex neurons from sporadic AD patients and age-matched controls. The average frequency of PCD,X in AD patients (8.60 +/- 1.20%) was almost three times higher (p  lt  0.01) than in the control group (2.96 +/- 1.20). However, consistent with previous studies, no mitotic cells were found in neurons in either AD or control brain, suggesting an intrinsic inability of post-mitotic neurons to divide. In view of the fact that it has been well-documented that neurons in AD can re-enter into the cell division cycle, the findings presented here of increased PCD advance the hypothesis that deregulation of the cell cycle may contribute to neuronal degeneration and subsequent cognitive deficits in AD.",
publisher = "Wiley-Blackwell, Malden",
journal = "Journal of Neurochemistry",
title = "Premature centromere division of the X chromosome in neurons in Alzheimer's disease",
volume = "106",
number = "5",
pages = "2218-2223",
doi = "10.1111/j.1471-4159.2008.05555.x"
}

Potparević, B., Živković, L., Đelić, N., Plećaš-Solarović, B., Smith, M. A.,& Bajić, V.. (2008). Premature centromere division of the X chromosome in neurons in Alzheimer's disease. in Journal of Neurochemistry
Wiley-Blackwell, Malden., 106(5), 2218-2223.
https://doi.org/10.1111/j.1471-4159.2008.05555.x

Potparević B, Živković L, Đelić N, Plećaš-Solarović B, Smith MA, Bajić V. Premature centromere division of the X chromosome in neurons in Alzheimer's disease. in Journal of Neurochemistry. 2008;106(5):2218-2223.
doi:10.1111/j.1471-4159.2008.05555.x .

Potparević, Biljana, Živković, Lada, Đelić, Ninoslav, Plećaš-Solarović, Bosiljka, Smith, Mark A., Bajić, Vladan, "Premature centromere division of the X chromosome in neurons in Alzheimer's disease" in Journal of Neurochemistry, 106, no. 5 (2008):2218-2223,
https://doi.org/10.1111/j.1471-4159.2008.05555.x . .

TY  - JOUR
AU  - Bajić, Vladan
AU  - Potparević, Biljana
AU  - Živković, Lada
AU  - Đelić, N
AU  - Smith, Mark A.
PY  - 2008
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1137
AB  - Chromosomal involvement is a legitimate, yet not well understood, feature of Alzheimer disease (AD). Firstly, AD affects more women than men. Secondly, the amyloid-β protein precursor genetic mutations, responsible for a cohort of familial AD cases, reside on chromosome 21, the same chromosome responsible for the developmental disorder Down's syndrome. Thirdly, lymphocytes from AD patients display a novel chromosomal phenotype, namely premature centromere separation (PCS). Other documented morphological phenomena associated with AD include the occurrence of micronuclei, aneuploidy, binucleation, telomere instability, and cell cycle re-entry protein expression. Based on these events, here we present a novel hypothesis that the time dimension of cell cycle re-entry in AD is highly regulated by centromere cohesion dynamics. In view of the fact that neurons can re-enter the cell division cycle, our hypothesis predicts that alterations in the signaling pathway leading to premature cell death in neurons is a consequence of altered regulation of the separation of centromeres as a function of time. It is well known that centromeres in the metaphase anaphase transition separate in a non-random, sequential order. This sequence has been shown to be deregulated in aging cells, various tumors, syndromes of chromosome instability, following certain chemical inductions, as well as in AD. Over time, premature chromosome separation is both a result of, and a driving force behind, further cohesion impairment, activation of cyclin dependent kinases, and mitotic catastrophe-a vicious circle resulting in cellular degeneration and death.
T2  - Bioscience Hypotheses
T1  - Is the time dimension of the cell cycle re-entry in AD regulated by centromere cohesion dynamics?
VL  - 1
IS  - 3
SP  - 156
EP  - 161
DO  - 10.1016/j.bihy.2008.03.006
ER  - 

@article{
author = "Bajić, Vladan and Potparević, Biljana and Živković, Lada and Đelić, N and Smith, Mark A.",
year = "2008",
abstract = "Chromosomal involvement is a legitimate, yet not well understood, feature of Alzheimer disease (AD). Firstly, AD affects more women than men. Secondly, the amyloid-β protein precursor genetic mutations, responsible for a cohort of familial AD cases, reside on chromosome 21, the same chromosome responsible for the developmental disorder Down's syndrome. Thirdly, lymphocytes from AD patients display a novel chromosomal phenotype, namely premature centromere separation (PCS). Other documented morphological phenomena associated with AD include the occurrence of micronuclei, aneuploidy, binucleation, telomere instability, and cell cycle re-entry protein expression. Based on these events, here we present a novel hypothesis that the time dimension of cell cycle re-entry in AD is highly regulated by centromere cohesion dynamics. In view of the fact that neurons can re-enter the cell division cycle, our hypothesis predicts that alterations in the signaling pathway leading to premature cell death in neurons is a consequence of altered regulation of the separation of centromeres as a function of time. It is well known that centromeres in the metaphase anaphase transition separate in a non-random, sequential order. This sequence has been shown to be deregulated in aging cells, various tumors, syndromes of chromosome instability, following certain chemical inductions, as well as in AD. Over time, premature chromosome separation is both a result of, and a driving force behind, further cohesion impairment, activation of cyclin dependent kinases, and mitotic catastrophe-a vicious circle resulting in cellular degeneration and death.",
journal = "Bioscience Hypotheses",
title = "Is the time dimension of the cell cycle re-entry in AD regulated by centromere cohesion dynamics?",
volume = "1",
number = "3",
pages = "156-161",
doi = "10.1016/j.bihy.2008.03.006"
}

Bajić, V., Potparević, B., Živković, L., Đelić, N.,& Smith, M. A.. (2008). Is the time dimension of the cell cycle re-entry in AD regulated by centromere cohesion dynamics?. in Bioscience Hypotheses, 1(3), 156-161.
https://doi.org/10.1016/j.bihy.2008.03.006

Bajić V, Potparević B, Živković L, Đelić N, Smith MA. Is the time dimension of the cell cycle re-entry in AD regulated by centromere cohesion dynamics?. in Bioscience Hypotheses. 2008;1(3):156-161.
doi:10.1016/j.bihy.2008.03.006 .

Bajić, Vladan, Potparević, Biljana, Živković, Lada, Đelić, N, Smith, Mark A., "Is the time dimension of the cell cycle re-entry in AD regulated by centromere cohesion dynamics?" in Bioscience Hypotheses, 1, no. 3 (2008):156-161,
https://doi.org/10.1016/j.bihy.2008.03.006 . .