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

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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.

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Acknowledgments

This study was supported by grants from Spain’s “Ministerio de Educación y Ciencia” SAF2009-13093, SAF2011-23631, BFU2010-19119 and BFU2010-22149 the “Fondo de Investigación Sanitaria”, and the “Instituto de Salud Carlos III” PI080400 and PS09/01789 (FEDER FOUNDS). 610RT0405 from Programa Iberoamericano de Ciencia y Tecnologia para el Desarrollo (CYTED). The authors would like to thank the “Generalitat de Catalunya” for supporting the research groups (2009/SGR00853) and the “Fundació la Marató TV3” (063230). The authors wish to thank the Language Assessment Service of the University of Barcelona for revising the manuscript.

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Authors and Affiliations

  1. Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Centros de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Institut de Biomedicina (IBUB), Universitat de Barcelona, Nucli Universitari de Pedralbes, 08028, Barcelona, Spain

    Felix Junyent, Javier G. Pizarro, Mercè Pallàs & Antoni Camins

  2. Unitat de Bioquimica, Facultat de Medicina i Ciències de la Salut, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Universitat Rovira i Virgili, C./St. Llorenç 21, 43201, Reus, Tarragona, Spain

    Jaume Folch & Felix Junyent

  3. Departament de Biologia Cel·lular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain

    Ester Verdaguer & Carme Auladell

  4. Departamento de Biología Celular y Molecular, C.U.C.B.A, Universidad de Guadalajara and División de Neurociencias, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada 800, Col. Independencia, 44340, Guadalajara, Jalisco, Mexico

    Carlos Beas-Zarate

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  1. Jaume Folch
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  8. Antoni Camins
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Correspondence to Antoni Camins.

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Folch, J., Junyent, F., Verdaguer, E. et al. Role of Cell Cycle Re-Entry in Neurons: A Common Apoptotic Mechanism of Neuronal Cell Death. Neurotox Res 22, 195–207 (2012). https://doi.org/10.1007/s12640-011-9277-4

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  • DOI: https://doi.org/10.1007/s12640-011-9277-4

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