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Luteolin protects rat PC 12 and C6 cells against MPP+ induced toxicity via an ERK dependent Keapl-Nrf2-ARE pathway

  • Conference paper
Neuropsychiatric Disorders An Integrative Approach

Part of the book series: Journal of Neural Transmission. Supplementa ((NEURALTRANS,volume 72))

Abstract

Oxidative stress is central to neuronal damage in neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. In consequence, activation of the cerebral oxidative stress defence is considered as a promising strategy of therapeutic intervention. Here we demonstrate that the flavone luteolin confers neuroprotection against oxidative stress via activation of the nuclear factor erythroid-2-related factor 2 (Nrf2), a transcription factor central to the maintenance of the cellular redox homeostasis. Luteolin protects rat neural PC12 and glial C6 cells from N-methyl-4-phenyl-pyridinium (MPP+) induced toxicity in vitro and effectively activates Nrf2 as shown by ARE-reporter gene assays. This protection critically depends on the activation of Nrf2 since downregulation of Nrf2 by shRNA completely abrogates the protection of luteolin in vitro. Furthermore, the neuroprotective effect of luteolin is abolished by the inhibition of the luteolininduced ERK1 /2-activation. Our results highlight the relevance of Nrf2 for neural cell survival conferred by flavones. In particular, we identified luteolin as a promising lead for the search of orally available, blood brain barrier permeable compounds to support the therapy of neurodegenerative disorders.

Authors contributed equally to the study

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Authors and Affiliations

  1. Federal Institute for Risk Assessment, Thielallee 88-92, 14195, Berlin, Germany

    PD Dr. rer. nat. M. E. Götz (Eurotoxicologist)

  2. Institute of Pharmacology, University Clinic of Schleswig-Holstein, Kiel, Germany

    C. J. Wruck, M. Claussen, G. Fuhrmann, L. Römer, A. Schulz, V. Waetzig, T. Herdegen & PD Dr. rer. nat. M. E. Götz (Eurotoxicologist)

  3. Institute of Anatomy, University of Schleswig-Holstein, Kiel, Germany

    C. J. Wruck & T. Pufe

  4. Institute of Nephrology, University Clinic of Schleswig-Holstein, Kiel, Germany

    M. Peipp

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  1. C. J. Wruck
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Editors and Affiliations

  1. Klinik und Poliklinik für Kinder- und Jugendpsychiatrie und Psychotherapie, Würzburg, Germany

    M. Gerlach

  2. Klinik und Poliklinik für Psychiatrie und Psychotherapie, Würzburg, Germany

    Jürgen Deckert

  3. Prince of Wales Medical Research Institute, Sydney, Australia

    K. Double

  4. Institut für Virologie und Immunobiologie, Würzburg, Germany

    E. Koutsilieri

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© 2007 Springer-Verlag

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Wruck, C.J. et al. (2007). Luteolin protects rat PC 12 and C6 cells against MPP+ induced toxicity via an ERK dependent Keapl-Nrf2-ARE pathway. In: Gerlach, M., Deckert, J., Double, K., Koutsilieri, E. (eds) Neuropsychiatric Disorders An Integrative Approach. Journal of Neural Transmission. Supplementa, vol 72. Springer, Vienna. https://doi.org/10.1007/978-3-211-73574-9_9

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  • DOI: https://doi.org/10.1007/978-3-211-73574-9_9

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