AI Article Synopsis
- BBB damage is linked to CNS diseases and can worsen cognitive function, but targeted therapies for preserving BBB integrity in I/R injury are not well-understood.* -
- This study reveals that circ-FoxO3 enhances autophagy by inhibiting mTORC1, helping to protect against BBB collapse during ischemia/reperfusion injury.* -
- Upregulation of circ-FoxO3 was observed in both human and mouse models, suggesting it could be a potential therapeutic target for treating neurological disorders related to BBB damage.*
Article Abstract
Blood-brain barrier (BBB) damage can be a result of central nervous system (CNS) diseases and may be a cause of CNS deterioration. However, there are still many unknowns regarding effective and targeted therapies for maintaining BBB integrity during ischemia/reperfusion (I/R) injury. In this study, we demonstrate that the circular RNA of FoxO3 (circ-FoxO3) promotes autophagy via mTORC1 inhibition to attenuate BBB collapse under I/R. Upregulation of circ-FoxO3 and autophagic flux were detected in brain microvessel endothelial cells in patients with hemorrhagic transformation and in mice models with middle cerebral artery occlusion/reperfusion. In vivo and in vitro studies indicated that circ-FoxO3 alleviated BBB damage principally by autophagy activation. Mechanistically, we found that circ-FoxO3 inhibited mTORC1 activity mainly by sequestering mTOR and E2F1, thus promoting autophagy to clear cytotoxic aggregates for improving BBB integrity. These results demonstrate that circ-FoxO3 plays a novel role in protecting against BBB damage, and that circ-FoxO3 may be a promising therapeutic target for neurological disorders associated with BBB damage.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899525 | PMC |
| http://dx.doi.org/10.1016/j.ymthe.2021.11.004 | DOI Listing |
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