Journal
AGING-US
Volume 3, Issue 9, Pages 846-851Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/aging.100382
Keywords
Alzheimer's disease; beta-amyloid; Cell cycle; Plk1; phosphorylation
Categories
Funding
- National Cancer Institute [K01 CA114401]
- Purdue University Center for Cancer Research
- National Science Foundation [MCB-1049693]
- Elsa U. Pardee Foundation [204937]
- Uniting against Lung Cancer [09107892]
- Direct For Biological Sciences
- Div Of Molecular and Cellular Bioscience [1049693] Funding Source: National Science Foundation
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Alzheimer's disease (AD) is a progressive and fatal brain disease, but the pathogenesis of AD is still not understood. Aberrant cell-cycle re-entry of neuronal cells is emerging as a potential pathological mechanism in AD. Polo-like kinase 1 (Plk1) is an established regulator of many cell cycle-related events. Interestingly, Plk1 is present in susceptible hippocampal and cortical neurons of AD patients but not age-matched controls. However, whether Plk1 is involved in the pathogenesis of AD remains elusive. In this study, we showed that Plk1 activity is elevated in AD patient brain as indicated by the increased phosphorylation signal of p150(Glued), a Plk1-specific substrate. Furthermore, we demonstrated that Plk1 is elevated during the cell-cycle re-entry of neuronal cells in an in vitro cell-culture model. Significantly, inhibition of Plk1 kinase activity or depletion of Plk1 by RNAi reduces beta-amyloid (A beta)-induced neuronal cell death. These results validate Plk1 as a possible target for AD therapy.
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