Implication of the transcription factor E2F-1 in the modulation of neuronal apoptosis

Verdaguer, Ester; de Arriba Susana, Garcia; Clemens, Allgaier; Pallas, Merce; Camins, Antoni


Neurodegenerative diseases as Alzheimer's disease, Parkinson's disease and other neurological disorders remain major problem worldwide since is currently no effective treatment. Thus, studying the mechanisms involved in neuronal apoptotic pathways is imperative if drugs that might stop or delay these disease processes are to be synthesized. In recent years it has become evident that mitochondria are key component of the neuronal apoptotic route. In addition to mitochondria, other intracellular components have been implicated in this process. Thus, DNA damage and re-entry into the cell cycle may constitute a common pathway in apoptosis in neurological diseases. The implication of cell cycle in neurodegenerative 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 re-entry into the cell cycle and, more specifically, an increase in the expression of E2F-I transcription role of DNA damage/repair as a potential mechanism in cell cycle re-entry. In this context, ataxia telangiectasia mutated protein could be the enzyme responsible for neuronal apoptosis activation. Furthermore, the potential routes involved in E2F-I induced apoptosis, p53dependent and p5 3 -independent, are similarly reviewed. Under this hypothesis, multiple pathways have been suggested, including the route of caspases. Finally, given the increasing experimental data on the neuroprotective and antiapoptotic effects of cyclin dependent kinase CDK inhibitory drugs, including flavopiridol, their application for the treatment of neurological disorders is proposed. (c) 2006 Elsevier Masson SAS. All rights reserved.

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Título según WOS: ID WOS:000249323900003 Not found in local WOS DB
Volumen: 61
Número: 7
Fecha de publicación: 2007
Página de inicio: 390
Página final: 399


Notas: ISI