Targeting Wnt signaling at the neuroimmune interface for dopaminergic neuroprotection/repair in Parkinson's disease

Francesca L'Episcopo, Cataldo Tirolo, Salvo Caniglia, Nuccio Testa, Maria Concetta Morale, Maria Francesca Serapide, Stefano Pluchino, Bianca Marchetti

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)13-26
Number of pages14
JournalJournal of Molecular Cell Biology
Volume6
Issue number1
DOIs
Publication statusPublished - Feb 2014

Keywords

  • dopaminergic neurons
  • neurodegeneration
  • neurogenesis
  • neuroinflammation
  • neuroprotection
  • Parkinson's disease
  • Wnt/β-catenin signaling

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology
  • Genetics

Fingerprint Dive into the research topics of 'Targeting Wnt signaling at the neuroimmune interface for dopaminergic neuroprotection/repair in Parkinson's disease'. Together they form a unique fingerprint.

Cite this