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

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.