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The Wnt Antagonist, Dickkopf-1, as a Target for the Treatment of Neurodegenerative Disorders

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Abstract

The canonical Wnt pathway contributes to the regulation of neuronal survival and homeostasis in the CNS. Recent evidence suggests that an increased expression of Dickkopf-1 (Dkk-1), a secreted protein that negatively modulates the canonical Wnt pathway, is causally related to processes of neurodegeneration in a number of CNS disorders, including Alzheimer’s disease (AD), brain ischemia and temporal lobe epilepsy (TLE). Dkk-1 induction precedes neuronal death in cellular and animal models of excitotoxicity, β-amyloid toxicity, transient global ischemia, and kainate-induced epilepsy. In addition, Dkk-1, which is barely visible in the healthy brain, is strongly induced in brain tissue from AD patients or from patients with TLE associated with hippocampal sclerosis. These data raise the attractive possibility that Dkk-1 antagonists or neutralizing antibodies behave as neuroprotective agents by rescuing the activity of the canonical Wnt pathway.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, University of Catania, Viale Andrea Doria 6, 95125, Catania, Italy

    Filippo Caraci & Agata Copani

  2. I.N.M. Neuromed, Località Camerelle, 86077, Pozzilli, Italy

    Carla Busceti, Francesca Biagioni, Federica Mastroiacovo, Giuseppe Battaglia, Valeria Bruno & Ferdinando Nicoletti

  3. Department of Neuropathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    Eleonora Aronica

  4. Department of Human Physiology and Pharmacology, University of Rome La Sapienza, 00185, Rome, Italy

    Irene Cappuccio, Valeria Bruno & Ferdinando Nicoletti

  5. Siena Biotech, Siena, Italy

    Andrea Caricasole

  6. I.B.B., CNR-Catania, 95125, Catania, Italy

    Agata Copani

Authors
  1. Filippo Caraci
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  2. Carla Busceti
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  9. Andrea Caricasole
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Correspondence to Filippo Caraci.

Additional information

Special issue article in honor of Anna Maria Giuffrida-Stella.

Agata Copani and Ferdinando Nicoletti—Co-senior authors.

Filippo Caraci—PhD Program in Neuropharmacology.

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Caraci, F., Busceti, C., Biagioni, F. et al. The Wnt Antagonist, Dickkopf-1, as a Target for the Treatment of Neurodegenerative Disorders. Neurochem Res 33, 2401–2406 (2008). https://doi.org/10.1007/s11064-008-9710-0

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  • DOI: https://doi.org/10.1007/s11064-008-9710-0

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