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

Document Type

Article

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

Publication Date

5-1-2003

Publication Title

Acta Neuropathologica

ISSN

00016322

Volume

105

Issue

5

First Page

524

Last Page

528

PubMed ID

12677454

Digital Object Identifier (DOI)

10.1007/s00401-003-0684-3

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