Review: Cell cycle aberrations and neurodegeneration

Bonda, David J.; Bajić, Vladan; Spremo-Potparević, Biljana; Casadesús, Gemma; Zhu, Xiongwei; Smith, Mark A.; Lee, Hyoung‐gon

doi:10.1111/j.1365-2990.2010.01064.x

Cited by 69 publications

(47 citation statements)

References 56 publications

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“…To date no mitosis has been found suggesting that affected neurons do not enter into the M phase of the cell cycle. Alterations such as PCD are considered to be probable proof of cell cycle re-entry [5,22,23] which may lead to premature cell death [39,45] and therefore to neurodegeneration.…”

Section: Discussionmentioning

confidence: 99%

“…A widely accepted opinion is that accumulation of DNA damage underlies the origin of diseases accompanied by aging, such as cancer and neurodegenerative diseases [24,37,38,39,40,41]. Two of the most investigated and likely main influences that introduce the cell in an aberrant cell cycle are endogenous oxidative stress and genomic instability [41].…”

Section: Discussionmentioning

confidence: 99%

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DNA Damage in Alzheimer Disease Lymphocytes and Its Relation to Premature Centromere Division

et al. 2013

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While Alzheimer disease (AD) is considered a neurodegenerative disorder, the importance of chromosome instability in non-neuronal cells is equally important, not only for shedding light on the etiology of the disease, but also for possible diagnostic purposes and monitoring the progress of the disease. Here, we evaluated the frequency of DNA damage and expression of premature centromere division (PCD) in peripheral blood lymphocytes of sporadic AD patients, age-matched and young controls. The results show that in male patients with AD, the frequencies of PCD and DNA damage were significantly greater (88%, p < 0.01 and 38%, p < 0.05, respectively) than in age-matched control group. AD females had significantly increased frequency of PCD (134%, p < 0.01) as well as a higher frequency of DNA damage (37%, p < 0.05). Ageing per se, both in males and females, shows significant increase of percentages of PCD (2.3 times, p < 0.01 and 2.8 times, p < 0.01, respectively) and DNA damage (63%, p < 0.01 and 50%, p < 0.01, respectively) comparing with young controls. In addition, a strong (R² = 0.873, n = 6) and significant (p < 0.01) correlation between the frequencies of PCD and DNA damage was found in all examined groups. We may conclude that the increases in both parameters evaluated in this study are not only associated with normal ageing processes, but are markedly and significantly intensified in AD pathogenesis. Thus, our data support the view that AD is a generalized systemic disease, at least as for the increased DNA damage and PCD incidence in peripheral blood cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

DNA Damage in Alzheimer Disease Lymphocytes and Its Relation to Premature Centromere Division

et al. 2013

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“…We have postulated in previous papers that APC/C in AD neurons might be regulated by cohesion and cohesion related proteins such as CDK 11 and MAD 2B, Bub R1, Securin [29,[80][81][82][83][84].…”

Section: Apc/c Cdh 1 Interacts With Prbmentioning

confidence: 99%

“…If the neurons become unbalanced, through the inhibition or excess activation of the late phase cell cycle proteins or the percentage of cells with the aneuploidogenic phenotype, then the cell is unable to cope with an increase in proteotoxic stress which then deregulates APP expression and Aβ accumulation. If the balance is not restored the cell undergoes cell cycle reentry which always leads to apoptosis and cell death [29,[31][32][33].…”

Section: Introductionmentioning

confidence: 99%

Late phase cell cycle proteins in Alzheimer’s disease: a possible target for therapy?

Bajić¹,

Bajić²,

Živković³

et al. 2016

J Syst Integr Neurosci

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Alzheimer's disease (AD) is represented by neuronal loss and this loss is correlated to a constant state of neuronal instability induced by intrinsic and extrinsic factors. In this paper data is presented regarding the possible roles of late phase cell cycle proteins in normal and affected neurons with the goal that understanding the mechanisms involved in the regulation of these proteins may represent a novel strategy for AD treatment. The results demonstrate a relative differential pattern of expression of certain proteins (APC/C, Mad1 and Mad2, Bub R1, Bub1, CDK 11, cohesin subunit Rad 21 and astrin) in the AD brain versus age matched controls, and it is suggested that targeting these proteins might translate into potential treatments for AD. Although the data presented here is of some interest, the ability to translate such information into clinical applications is often a challenge.

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“…Once in this phase, cells are deemed terminally differentiated, meaning they are not capable of re-entering the cell cycle. (61,62) It is in this capacity that vulnerable neurones are affected. As increasing evidence indicates, cells that exist in G0, and thus are no longer mitotically active, become wrongly reactivated in AD and other NDDs, and are forced through a cell cycle that they are no longer capable of completing.…”

Section: Dna Damage and Nddmentioning

confidence: 99%

New Insight in The Molecular Mechanisms of Neurodegenerative Disease

2018

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B ACKGROUND:Redox and proteotoxic stress contributes to age-dependent accumulation of dysfunctional mitochondria and protein aggregates, and is associated with neurodegeneration. The free radical theory of aging inspired many studies using reactive species scavengers such as alpha-tocopherol, ascorbate and coenzyme-Q to suppress the initiation of oxidative stress. However, clinical trials have had limited success in the treatment of neurodegenerative diseases (NDDs). CONTENT:The misfolding and aggregation of specific proteins is a seminal occurrence in a remarkable variety of NDDs. In Alzheimer's disease, the two principal aggregating proteins are β-amyloid (Aβ) and tau. The abnormal assemblies formed by conformational variants of these proteins range in size from small oligomers to the characteristic lesions that are visible by optical microscopy, such as senile plaques and neurofibrillary tangles. Pathologic similarities with prion disease suggest that the formation and spread of these proteinaceous lesions might involve a common molecular mechanism, corruptive protein templating. The accumulation of redox modified proteins or organelles cannot be reversed by oxidant intercepting antioxidants and must then be removed by alternative mechanisms. Autophagy serves this essential function in removing damaged or dysfunctional proteins and organelles thus preserving neuronal function and survival.SUMMARY: Senescent cells and their senescenceassociated secretory phenotypes (SASPs) may constitute a novel, understudied, and potentially important contributor to neuro-inflammation and subsequent neurodegeneration. Characterization of cellular senescence in the brain could uncover novel therapeutic targets for the prevention and treatment of chronic age-related NDDs. KEYwORDS

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Review: Cell cycle aberrations and neurodegeneration

Cited by 69 publications

References 56 publications

DNA Damage in Alzheimer Disease Lymphocytes and Its Relation to Premature Centromere Division

DNA Damage in Alzheimer Disease Lymphocytes and Its Relation to Premature Centromere Division

Late phase cell cycle proteins in Alzheimer’s disease: a possible target for therapy?

New Insight in The Molecular Mechanisms of Neurodegenerative Disease

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