Research Paper|Volume 3, Issue 9|pp 846—851

Inhibition of Polo-like kinase 1 reduces beta-amyloid-induced neuronal cell death in Alzheimer's disease

Bing Song¹, Korbin Davis², X. Shawn Liu², Hyoung-gon Lee⁴, Mark Smith⁴, Xiaoqi Liu^2,³

¹Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA
²Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA
³Purdue Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA
⁴Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA

Received: September 5, 2011Accepted: September 13, 2011Published: September 13, 2011

Copyright: © 2011 Song et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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 β-amyloid (Aβ)-induced neuronal cell death. These results validate Plk1 as a possible target for AD therapy.