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Chemokine CXCL12 in neurodegenerative diseases: an SOS signal for stem cell-based repair

Journal

TRENDS IN NEUROSCIENCES
Volume 35, Issue 10, Pages 619-628

Publisher

ELSEVIER SCIENCE LONDON
DOI: 10.1016/j.tins.2012.06.003

Keywords

CXCL12; CXCR4; neurodegeneration; stem cells; tissue repair

Categories

Funding

  1. Voices Against Brain Cancer, Ohio Cancer Research Associates
  2. National Institutes of Health (NIH) K99/R00 Pathway to Independence Award [CA157948]
  3. James D. Foundation
  4. NIH [CA112958, CA116659, CA154130, R01NS32151, K24NS51400, R21NS74820]
  5. National Multiple Sclerosis (MS) Society
  6. Williams Family Fund for MS research

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The dynamic relation between stem cells and their niche governs self-renewal and progenitor cell deployment. The chemokine CXCL12 (C-X-C motif ligand 12) and its signaling receptor CXCR4 (C-X-C motif receptor 4) represent an important pathway that regulates homing and maintenance of stem cells in neural niches. Neural stem cells (NSCs) reside in specific niches where communication with blood vessels is regulated by CXCL12. In neurodegenerative diseases and brain tumors, reactive vasculature forms in response to diseased tissues to create new niches that secrete CXCL12, enhancing the recruitment of neural progenitor cells (NPCs) to lesion sites via long-range migration. These observations suggest that the CXCL12 CXCR4 axis maintains NSCs and serves as an emergent salvage signal for initiating endogenous stem cell-based tissue repair.

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