AI Article Synopsis
- Vascular dysfunction and compromised blood-brain barrier (BBB) integrity are linked to aging and diseases, particularly through the complement C3a/C3a receptor (C3a/C3aR) axis.
- Propson et al. examined how C3aR signaling in endothelial cells affects neurovascular inflammation and BBB permeability in mouse models of aging and neurodegeneration.
- Their findings suggest that blocking C3aR could mitigate age-related microglial reactivity and BBB damage, pointing to complement inhibitors as a potential treatment for vascular issues in the brain.
Article Abstract
Vascular dysfunction resulting in compromised blood-brain barrier (BBB) integrity is evident in aging and disease. Although the complement C3a/C3a receptor (C3a/C3aR) axis influences normal brain aging and disease progression, the mechanisms governing endothelial C3aR-mediated neurovascular inflammation and BBB permeability remain unexplored. In this issue of the JCI, Propson et al. investigated endothelial C3a/C3aR signaling in normal, aged, and neurodegenerative mouse models. Endothelial C3aR signaling modulated age-dependent increases in VCAM1, initiated peripheral lymphocyte infiltration, and enhanced microglial activity. Increased calcium release downstream of C3aR signaling disrupted the vascular endothelial cadherin (VE-cadherin) junctions, increased BBB permeability, and degraded vascular structure and function. Mice lacking C3aR (C3ar1-/-) and mice treated with a C3aR antagonist showed attenuated age-related microglial reactivity and neurodegeneration. These results confirm that complement-mediated signaling impacts vascular health and BBB function in normal aging and neurodegenerative disease, suggesting that complement inhibitors represent a therapeutic option for cerebral microvascular dysfunction.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773380 | PMC |
| http://dx.doi.org/10.1172/JCI144348 | DOI Listing |
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