Ectopic localization of phosphorylated histone H3 in Alzheimer's disease: A mitotic catastrophe?

Osamu Ogawa; Xiongwei Zhu; Hyoung Gon Lee; Arun Raina; Mark E. Obrenovich; Robert Bowser; Hossein A. Ghanbari; Rudolph J. Castellani; George Perry; Mark A. Smith

doi:10.1007/s00401-003-0684-3

Ectopic localization of phosphorylated histone H3 in Alzheimer's disease: A mitotic catastrophe?

Osamu Ogawa, Xiongwei Zhu, Hyoung Gon Lee, Arun Raina, Mark E. Obrenovich, Robert Bowser, Hossein A. Ghanbari, Rudolph J. Castellani, George Perry, Mark A. Smith^*

^*Corresponding author for this work

Pathology

Research output: Contribution to journal › Article › peer-review

155 Scopus citations

Abstract

Despite their terminally differentiated status, vulnerable neurons in Alzheimer's disease (AD) display evidence of cell cycle activation, suggesting that mitotic dysfunction may be important in disease pathogenesis. To further delineate the role of mitotic processes in disease pathogenesis, we investigated phosphorylated histone H3, a key component involved in chromosome compaction during cell division. Consistent with an activation of the mitotic machinery, we found an increase in phosphorylated histone H3 in hippocampal neurons in AD. However, rather than within the nucleus as in actively dividing cells, activated phosphorylated histone H3 in AD is restricted to the neuronal cytoplasm despite activation of the mitotic machinery. Therefore, the aberrant cytoplasmic localization of phosphorylated histone H3 indicates a mitotic catastrophe that leads to neuronal dysfunction and neurodegeneration in AD.

Original language	English (US)
Pages (from-to)	524-528
Number of pages	5
Journal	Acta Neuropathologica
Volume	105
Issue number	5
DOIs	https://doi.org/10.1007/s00401-003-0684-3
State	Published - May 1 2003

Funding

Acknowledgements This work was supported by grants funding from the National Institutes of Health (NS38648) and the Alzheimer’s Association (ZEN-99–1789).

Keywords

Alzheimer's disease
Cell cycle
Histone H3
Mitosis
Phosphorylation

ASJC Scopus subject areas

Clinical Neurology
Cellular and Molecular Neuroscience
Pathology and Forensic Medicine

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title = "Ectopic localization of phosphorylated histone H3 in Alzheimer's disease: A mitotic catastrophe?",

abstract = "Despite their terminally differentiated status, vulnerable neurons in Alzheimer's disease (AD) display evidence of cell cycle activation, suggesting that mitotic dysfunction may be important in disease pathogenesis. To further delineate the role of mitotic processes in disease pathogenesis, we investigated phosphorylated histone H3, a key component involved in chromosome compaction during cell division. Consistent with an activation of the mitotic machinery, we found an increase in phosphorylated histone H3 in hippocampal neurons in AD. However, rather than within the nucleus as in actively dividing cells, activated phosphorylated histone H3 in AD is restricted to the neuronal cytoplasm despite activation of the mitotic machinery. Therefore, the aberrant cytoplasmic localization of phosphorylated histone H3 indicates a mitotic catastrophe that leads to neuronal dysfunction and neurodegeneration in AD.",

keywords = "Alzheimer's disease, Cell cycle, Histone H3, Mitosis, Phosphorylation",

author = "Osamu Ogawa and Xiongwei Zhu and Lee, {Hyoung Gon} and Arun Raina and Obrenovich, {Mark E.} and Robert Bowser and Ghanbari, {Hossein A.} and Castellani, {Rudolph J.} and George Perry and Smith, {Mark A.}",

note = "Funding Information: Acknowledgements This work was supported by grants funding from the National Institutes of Health (NS38648) and the Alzheimer{\textquoteright}s Association (ZEN-99–1789).",

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doi = "10.1007/s00401-003-0684-3",

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T1 - Ectopic localization of phosphorylated histone H3 in Alzheimer's disease

T2 - A mitotic catastrophe?

AU - Ogawa, Osamu

AU - Zhu, Xiongwei

AU - Lee, Hyoung Gon

AU - Raina, Arun

AU - Obrenovich, Mark E.

AU - Bowser, Robert

AU - Ghanbari, Hossein A.

AU - Castellani, Rudolph J.

AU - Perry, George

AU - Smith, Mark A.

N1 - Funding Information: Acknowledgements This work was supported by grants funding from the National Institutes of Health (NS38648) and the Alzheimer’s Association (ZEN-99–1789).

PY - 2003/5/1

Y1 - 2003/5/1

N2 - Despite their terminally differentiated status, vulnerable neurons in Alzheimer's disease (AD) display evidence of cell cycle activation, suggesting that mitotic dysfunction may be important in disease pathogenesis. To further delineate the role of mitotic processes in disease pathogenesis, we investigated phosphorylated histone H3, a key component involved in chromosome compaction during cell division. Consistent with an activation of the mitotic machinery, we found an increase in phosphorylated histone H3 in hippocampal neurons in AD. However, rather than within the nucleus as in actively dividing cells, activated phosphorylated histone H3 in AD is restricted to the neuronal cytoplasm despite activation of the mitotic machinery. Therefore, the aberrant cytoplasmic localization of phosphorylated histone H3 indicates a mitotic catastrophe that leads to neuronal dysfunction and neurodegeneration in AD.

AB - Despite their terminally differentiated status, vulnerable neurons in Alzheimer's disease (AD) display evidence of cell cycle activation, suggesting that mitotic dysfunction may be important in disease pathogenesis. To further delineate the role of mitotic processes in disease pathogenesis, we investigated phosphorylated histone H3, a key component involved in chromosome compaction during cell division. Consistent with an activation of the mitotic machinery, we found an increase in phosphorylated histone H3 in hippocampal neurons in AD. However, rather than within the nucleus as in actively dividing cells, activated phosphorylated histone H3 in AD is restricted to the neuronal cytoplasm despite activation of the mitotic machinery. Therefore, the aberrant cytoplasmic localization of phosphorylated histone H3 indicates a mitotic catastrophe that leads to neuronal dysfunction and neurodegeneration in AD.

KW - Alzheimer's disease

KW - Cell cycle

KW - Histone H3

KW - Mitosis

KW - Phosphorylation

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Ectopic localization of phosphorylated histone H3 in Alzheimer's disease: A mitotic catastrophe?

Abstract

Funding

Keywords

ASJC Scopus subject areas

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