The Wnt antagonist, Dickkopf-1, as a target for the treatment of neurodegenerative disorders

Filippo Caraci; Carla Busceti; Francesca Biagioni; Eleonora Aronica; Federica Mastroiacovo; Irene Cappuccio; Giuseppe Battaglia; Valeria Bruno; Andrea Caricasole; Agata Copani; Ferdinando Nicoletti

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

The Wnt antagonist, Dickkopf-1, as a target for the treatment of neurodegenerative disorders

Filippo Caraci, Carla Busceti, Francesca Biagioni, Eleonora Aronica, Federica Mastroiacovo, Irene Cappuccio, Giuseppe Battaglia, Valeria Bruno, Andrea Caricasole, Agata Copani, Ferdinando Nicoletti

Research output: Contribution to journal › Review article › Academic › peer-review

53 Citations (Scopus)

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

Original language	English
Pages (from-to)	2401-2406
Journal	Neurochemical research
Volume	33
Issue number	12
DOIs	https://doi.org/10.1007/s11064-008-9710-0
Publication status	Published - 2008

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

Cite this

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title = "The Wnt antagonist, Dickkopf-1, as a target for the treatment of neurodegenerative disorders",

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",

author = "Filippo Caraci and Carla Busceti and Francesca Biagioni and Eleonora Aronica and Federica Mastroiacovo and Irene Cappuccio and Giuseppe Battaglia and Valeria Bruno and Andrea Caricasole and Agata Copani and Ferdinando Nicoletti",

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T1 - The Wnt antagonist, Dickkopf-1, as a target for the treatment of neurodegenerative disorders

AU - Caraci, Filippo

AU - Busceti, Carla

AU - Biagioni, Francesca

AU - Aronica, Eleonora

AU - Mastroiacovo, Federica

AU - Cappuccio, Irene

AU - Battaglia, Giuseppe

AU - Bruno, Valeria

AU - Caricasole, Andrea

AU - Copani, Agata

AU - Nicoletti, Ferdinando

PY - 2008

Y1 - 2008

N2 - 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

AB - 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

U2 - https://doi.org/10.1007/s11064-008-9710-0

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

M3 - Review article

C2 - 18427981

SN - 0364-3190

VL - 33

SP - 2401

EP - 2406

JO - Neurochemical research

JF - Neurochemical research

IS - 12

ER -