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, beta-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.

The Wnt Antagonist, Dickkopf-1, as a Target for the Treatment of Neurodegenerative Disorders / Filippo, Caraci; Carla, Busceti; Francesca, Biagioni; Eleonora, Aronica; Federica, Mastroiacovo; Cappuccio, Irene; Battaglia, Giuseppe; Bruno, Valeria Maria Gloria; Andrea, Caricasole; Agata, Copani; Nicoletti, Ferdinando. - In: NEUROCHEMICAL RESEARCH. - ISSN 0364-3190. - STAMPA. - 33:12(2008), pp. 2401-2406. [10.1007/s11064-008-9710-0]

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

CAPPUCCIO, Irene;BATTAGLIA, Giuseppe;BRUNO, Valeria Maria Gloria;NICOLETTI, Ferdinando
2008

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, beta-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.
2008
beta-catenin; canonical wnt pathway; dkk-1; lithium; neurodegeneration; neuronal death; β-catenin
01 Pubblicazione su rivista::01a Articolo in rivista
The Wnt Antagonist, Dickkopf-1, as a Target for the Treatment of Neurodegenerative Disorders / Filippo, Caraci; Carla, Busceti; Francesca, Biagioni; Eleonora, Aronica; Federica, Mastroiacovo; Cappuccio, Irene; Battaglia, Giuseppe; Bruno, Valeria Maria Gloria; Andrea, Caricasole; Agata, Copani; Nicoletti, Ferdinando. - In: NEUROCHEMICAL RESEARCH. - ISSN 0364-3190. - STAMPA. - 33:12(2008), pp. 2401-2406. [10.1007/s11064-008-9710-0]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/364935
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