A Systematic Review of WNT Signaling in Endothelial Cell Oligodendrocyte Interactions: Potential Relevance to Cerebral Small Vessel Disease

Narek Manukjan, Zubair Ahmed, Daniel Fulton, W. Matthijs Blankesteijn, Sebastien Foulquier*

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

Abstract

Key pathological features of cerebral small vessel disease (cSVD) include impairment of the blood brain barrier (BBB) and the progression of white matter lesions (WMLs) amongst other structural lesions, leading to the clinical manifestations of cSVD. The function of endothelial cells (ECs) is of major importance to maintain a proper BBB. ECs interact with several cell types to provide structural and functional support to the brain. Oligodendrocytes (OLs) myelinate axons in the central nervous system and are crucial in sustaining the integrity of white matter. The interplay between ECs and OLs and their precursor cells (OPCs) has received limited attention yet seems of relevance for the study of BBB dysfunction and white matter injury in cSVD. Emerging evidence shows a crosstalk between ECs and OPCs/OLs, mediated by signaling through the Wingless and Int-1 (WNT)/beta-catenin pathway. As the latter is involved in EC function (e.g., angiogenesis) and oligodendrogenesis, we reviewed the role of WNT/beta-catenin signaling for both cell types and performed a systematic search to identify studies describing a WNT-mediated interplay between ECs and OPCs/OLs. Dysregulation of this interaction may limit remyelination of WMLs and render the BBB leaky, thereby initiating a vicious neuroinflammatory cycle. A better understanding of the role of this signaling pathway in EC-OL crosstalk is essential in understanding cSVD development.

Original languageEnglish
Article number1545
Number of pages16
JournalCells
Volume9
Issue number6
DOIs
Publication statusPublished - Jun 2020

Keywords

  • cerebral small vessel disease
  • WNT
  • beta-catenin
  • oligodendrocytes
  • oligodendrocyte precursor cells
  • endothelial cells
  • BLOOD-BRAIN-BARRIER
  • VASCULAR COGNITIVE IMPAIRMENT
  • TROPHIC SUPPORT
  • BETA-CATENIN
  • MYELIN
  • HYPERTENSION
  • DYNAMICS
  • STROKE
  • MODEL
  • PATHOPHYSIOLOGY

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