Targeting Wnt Signaling at the Neuroimmune Interface for Dopaminergic Neuroprotection/repair in Parkinson's Disease

Overview

Journal J Mol Cell Biol

Publisher Oxford University Press

Specialty Molecular Biology

Date 2014 Jan 17

PMID 24431301

Citations 41

Authors

Francesca LEpiscopo

Cataldo Tirolo

Salvo Caniglia

Nuccio Testa

Maria Concetta Morale

Maria Francesca Serapide

Stefano Pluchino

Bianca Marchetti

Affiliations

Soon will be listed here.

Abstract

During the past three decades, the Wingless-type MMTV integration site (Wnt) signaling cascade has emerged as an essential system regulating multiple processes in developing and adult brain. Accumulating evidence points to a dysregulation of Wnt signaling in major neurodegenerative pathologies including Parkinson's disease (PD), a common neurodegenerative disorder characterized by the progressive loss of midbrain dopaminergic (mDA) neurons and deregulated activation of astrocytes and microglia. This review highlights the emerging link between Wnt signaling and key inflammatory pathways during mDA neuron damage/repair in PD progression. In particular, we summarize recent evidence documenting that aging and neurotoxicant exposure strongly antagonize Wnt/β-catenin signaling in mDA neurons and subventricular zone (SVZ) neuroprogenitors via astrocyte-microglial interactions. Dysregulation of the crosstalk between Wnt/β-catenin signaling and anti-oxidant/anti-inflammatory pathways delineate novel mechanisms driving the decline of SVZ plasticity with age and the limited nigrostriatal dopaminergic self-repair in PD. These findings hold a promise in developing therapies that target Wnt/β-catenin signaling to enhance endogenous restoration and neuronal outcome in age-dependent diseases, such as PD.

Citing Articles

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The Molecular Basis of Wnt/-Catenin Signaling Pathways in Neurodegenerative Diseases.

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Stem Cell Transplantation for Parkinson's Disease: Current Challenges and Perspectives.

Zeng X, Qin H Aging Dis. 2022; 13(6):1652-1663.

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Small Extracellular Vesicles Secreted by Nigrostriatal Astrocytes Rescue Cell Death and Preserve Mitochondrial Function in Parkinson's Disease.

Leggio L, LEpiscopo F, Magri A, Ulloa-Navas M, Paterno G, Vivarelli S Adv Healthc Mater. 2022; 11(20):e2201203.

PMID: 35856921 PMC: 11468249. DOI: 10.1002/adhm.202201203.

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