Ectopic localization of phosphorylated histone H3 in Alzheimer's disease: a mitotic catastrophe?
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.
Ogawa
Osamu
O
Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA.
Zhu
Xiongwei
X
Lee
Hyoung-Gon
HG
Raina
Arun
A
Obrenovich
Mark E
ME
Bowser
Robert
R
Ghanbari
Hossein A
HA
Castellani
Rudolph J
RJ
Perry
George
G
Smith
Mark A
MA
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D008938:Mitosis; D010446:Peptide Fragments; D010766:Phosphorylation; D017966:Pyramidal Cells / Q000378:metabolism
D006657:Histones; D010446:Peptide Fragments