Neurotoxicity Research

, Volume 22, Issue 3, pp 195–207 | Cite as

Role of Cell Cycle Re-Entry in Neurons: A Common Apoptotic Mechanism of Neuronal Cell Death

  • Jaume Folch
  • Felix Junyent
  • Ester Verdaguer
  • Carme Auladell
  • Javier G. Pizarro
  • Carlos Beas-Zarate
  • Mercè Pallàs
  • Antoni Camins
Review

Abstract

Currently, there is no effective treatment for neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease. Thus, a major focus of neuroscience research is to examine the mechanisms involved in neuronal loss in order to identify potential drug targets. Recent results indicate that DNA damage and re-entry into the cell cycle may constitute a common pathway in apoptosis in neurological diseases. The role of the cell cycle in such disorders is supported by data on the brain of patients who showed an increase in cell-cycle protein expression. Indeed, studies performed in neuronal cell preparations indicate that oxidative stress could be the main mechanism responsible for cell cycle re-entry. DNA damage and repair after oxidative stress may activate the enzyme ataxia telangiectasia mutated, which is a cell-cycle regulator. Once the cell cycle is activated, the increase in the expression of transcription factor E2F-1 could induce neuronal apoptosis. Furthermore, the potential routes involved in E2F-1 induced apoptosis could be p53-dependent or p53-independent. Under this E2F-1 hypothesis of cell death, multiple mitochondria-dependent pathways may be activated, including caspase and caspase-independent signaling cascades. Finally, given that cyclin-dependent kinase inhibitory drugs have neuroprotective and anti-apoptotic effects in experimental models, their potential application for the treatment of neurological disorders should be taken into account.

Keywords

E2F-1 Cyclin-dependent kinases CDK5 p53 Alzheimer’s disease Parkinson’s disease 

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Jaume Folch
    • 2
  • Felix Junyent
    • 1
    • 2
  • Ester Verdaguer
    • 3
  • Carme Auladell
    • 3
  • Javier G. Pizarro
    • 1
  • Carlos Beas-Zarate
    • 4
  • Mercè Pallàs
    • 1
  • Antoni Camins
    • 1
  1. 1.Unitat de Farmacologia i Farmacognòsia, Facultat de FarmàciaCentros de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Institut de Biomedicina (IBUB), Universitat de Barcelona, Nucli Universitari de PedralbesBarcelonaSpain
  2. 2.Unitat de Bioquimica, Facultat de Medicina i Ciències de la SalutCentro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Universitat Rovira i VirgiliReusSpain
  3. 3.Departament de Biologia Cel·lular, Facultat de BiologiaUniversitat de BarcelonaBarcelonaSpain
  4. 4.Departamento de Biología Celular y Molecular, C.U.C.B.AUniversidad de Guadalajara and División de Neurociencias, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS)GuadalajaraMexico

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