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Wnt/β-Catenin Signaling Pathway Governs a Full Program for Dopaminergic Neuron Survival, Neurorescue and Regeneration in the MPTP Mouse Model of Parkinson’s Disease

1
Department of Biomedical and Biotechnological Sciences (BIOMETEC), Pharmacology Section, Medical School, University of Catania, Via Santa Sofia 97, 95123 Catania, Italy
2
OASI Research Institute-IRCCS, Section of Neuropharmacology, Via Conte Ruggero 73, 94018 Troina (EN), Italy
Int. J. Mol. Sci. 2018, 19(12), 3743; https://doi.org/10.3390/ijms19123743
Received: 17 October 2018 / Revised: 12 November 2018 / Accepted: 17 November 2018 / Published: 24 November 2018
(This article belongs to the Special Issue Neuron Cell Death)
Wingless-type mouse mammary tumor virus (MMTV) integration site (Wnt) signaling is one of the most critical pathways in developing and adult tissues. In the brain, Wnt signaling contributes to different neurodevelopmental aspects ranging from differentiation to axonal extension, synapse formation, neurogenesis, and neuroprotection. Canonical Wnt signaling is mediated mainly by the multifunctional β-catenin protein which is a potent co-activator of transcription factors such as lymphoid enhancer factor (LEF) and T-cell factor (TCF). Accumulating evidence points to dysregulation of Wnt/β-catenin signaling in major neurodegenerative disorders. This review highlights a Wnt/β-catenin/glial connection in Parkinson’s disease (PD), the most common movement disorder characterized by the selective death of midbrain dopaminergic (mDAergic) neuronal cell bodies in the subtantia nigra pars compacta (SNpc) and gliosis. Major findings of the last decade document that Wnt/β-catenin signaling in partnership with glial cells is critically involved in each step and at every level in the regulation of nigrostriatal DAergic neuronal health, protection, and regeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD, focusing on Wnt/β-catenin signaling to boost a full neurorestorative program in PD. View Full-Text
Keywords: Parkinson’s disease; cell death; dopaminergic neurons; Wnt/β-catenin signaling; glia–neuron cross-talk; neurodegeneration; neuroprotection; neurorepair Parkinson’s disease; cell death; dopaminergic neurons; Wnt/β-catenin signaling; glia–neuron cross-talk; neurodegeneration; neuroprotection; neurorepair
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Marchetti, B. Wnt/β-Catenin Signaling Pathway Governs a Full Program for Dopaminergic Neuron Survival, Neurorescue and Regeneration in the MPTP Mouse Model of Parkinson’s Disease. Int. J. Mol. Sci. 2018, 19, 3743.

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