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The neuronal cell cycle as a mechanism of pathogenesis in Alzheimer's disease.

Currais A, Hortobágyi T, Soriano S - Aging (Albany NY) (2009)

Bottom Line: Nevertheless, expression of cell cycle modulators persists after neuronal differentiation and is upregulated under stress conditions, such as trophic factor deprivation, oxidative stress and the presence of DNA damaging agents.However, the physiological and pathogenic implications of a putative neuronal cell cycle are far from clear.Here, we discuss the notion of the neuronal cell cycle as a mediator of cell death, with particular emphasis on Alzheimer's disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, MRC Centre for Neurodegeneration Research, Institute of Psychiatry, King's College London, London SE5 8AF, UK.

ABSTRACT
Differentiated neurons display specific biochemical, physiological and morphological properties that apparently prevent them from further cell division. Nevertheless, expression of cell cycle modulators persists after neuronal differentiation and is upregulated under stress conditions, such as trophic factor deprivation, oxidative stress and the presence of DNA damaging agents. This apparent reactivation of the cell cycle has been postulated as a sine qua non for neuronal death in response to those stress conditions, particularly in Alzheimer's disease. However, the physiological and pathogenic implications of a putative neuronal cell cycle are far from clear. Here, we discuss the notion of the neuronal cell cycle as a mediator of cell death, with particular emphasis on Alzheimer's disease.

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(a) Tau                                            accumulates and is hyperphosphorylated at S202/T205 and S396/S404 in                                            primary neurons from PS1 M146V mice compared to wild-type controls. Shown is a Western blot analysis of Triton                                            X-100 soluble lysates. Antibodies used were AT8 (phosphorylated S202/T205),                                            PHF-1 (phosphorylated S396/S404) and DAKO (total tau); (b) Tau                                            phosphorylation at S202/T205 is detectable exclusively in neurons                                            expressing cyclin A, highlighting the importance of tau phosphorylation                                            dynamics in the neuronal cell cycle.
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Figure 2: (a) Tau accumulates and is hyperphosphorylated at S202/T205 and S396/S404 in primary neurons from PS1 M146V mice compared to wild-type controls. Shown is a Western blot analysis of Triton X-100 soluble lysates. Antibodies used were AT8 (phosphorylated S202/T205), PHF-1 (phosphorylated S396/S404) and DAKO (total tau); (b) Tau phosphorylation at S202/T205 is detectable exclusively in neurons expressing cyclin A, highlighting the importance of tau phosphorylation dynamics in the neuronal cell cycle.

Mentions: Interestingly, and consistent with the notion that a highly specialized cytoskeleton may be the origin of cell cycle-driven apoptosis by simply preventing a cycling neuron from undergoing chromosome segregation and cytokinesis, we have found profound abnormalities in tau homeostasis in our PS1 FAD mouse model. Specifically, tau is hyperphosphorylated in mitotic epitopes in these mice (Figure 2a) and, perhaps more importantly, nuclear expression of cyclin A appears to correlate with the tau phosphorylation at S202/T205 (Figure 2b).


The neuronal cell cycle as a mechanism of pathogenesis in Alzheimer's disease.

Currais A, Hortobágyi T, Soriano S - Aging (Albany NY) (2009)

(a) Tau                                            accumulates and is hyperphosphorylated at S202/T205 and S396/S404 in                                            primary neurons from PS1 M146V mice compared to wild-type controls. Shown is a Western blot analysis of Triton                                            X-100 soluble lysates. Antibodies used were AT8 (phosphorylated S202/T205),                                            PHF-1 (phosphorylated S396/S404) and DAKO (total tau); (b) Tau                                            phosphorylation at S202/T205 is detectable exclusively in neurons                                            expressing cyclin A, highlighting the importance of tau phosphorylation                                            dynamics in the neuronal cell cycle.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2806021&req=5

Figure 2: (a) Tau accumulates and is hyperphosphorylated at S202/T205 and S396/S404 in primary neurons from PS1 M146V mice compared to wild-type controls. Shown is a Western blot analysis of Triton X-100 soluble lysates. Antibodies used were AT8 (phosphorylated S202/T205), PHF-1 (phosphorylated S396/S404) and DAKO (total tau); (b) Tau phosphorylation at S202/T205 is detectable exclusively in neurons expressing cyclin A, highlighting the importance of tau phosphorylation dynamics in the neuronal cell cycle.
Mentions: Interestingly, and consistent with the notion that a highly specialized cytoskeleton may be the origin of cell cycle-driven apoptosis by simply preventing a cycling neuron from undergoing chromosome segregation and cytokinesis, we have found profound abnormalities in tau homeostasis in our PS1 FAD mouse model. Specifically, tau is hyperphosphorylated in mitotic epitopes in these mice (Figure 2a) and, perhaps more importantly, nuclear expression of cyclin A appears to correlate with the tau phosphorylation at S202/T205 (Figure 2b).

Bottom Line: Nevertheless, expression of cell cycle modulators persists after neuronal differentiation and is upregulated under stress conditions, such as trophic factor deprivation, oxidative stress and the presence of DNA damaging agents.However, the physiological and pathogenic implications of a putative neuronal cell cycle are far from clear.Here, we discuss the notion of the neuronal cell cycle as a mediator of cell death, with particular emphasis on Alzheimer's disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, MRC Centre for Neurodegeneration Research, Institute of Psychiatry, King's College London, London SE5 8AF, UK.

ABSTRACT
Differentiated neurons display specific biochemical, physiological and morphological properties that apparently prevent them from further cell division. Nevertheless, expression of cell cycle modulators persists after neuronal differentiation and is upregulated under stress conditions, such as trophic factor deprivation, oxidative stress and the presence of DNA damaging agents. This apparent reactivation of the cell cycle has been postulated as a sine qua non for neuronal death in response to those stress conditions, particularly in Alzheimer's disease. However, the physiological and pathogenic implications of a putative neuronal cell cycle are far from clear. Here, we discuss the notion of the neuronal cell cycle as a mediator of cell death, with particular emphasis on Alzheimer's disease.

Show MeSH
Related in: MedlinePlus