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 Liu2,3, ,

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

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

https://doi.org/10.18632/aging.100382
How to Cite

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 p150Glued, 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.

Abbreviations

AD: Alzheimer's disease; BrdU: 5-bromo-2′-deoxy-uridine; DAPI: 4′6′-diamidino-2-phenylindole; IF: immunofluorescence; IHC: immunohistochemistry; IP: immunoprecipitation; NGF: Nerve growth factor; Plk1: polo-like kinase 1; RNAi: RNA interference; Aϐ: beta-amyloid.