The elucidation of the dual role of Beclin-1 in ischemic stroke through systems biology modeling
Summary: Beclin-1 plays a pivotal role in the interplay between autophagy and apoptosis in ischemic stroke, influencing both cell survival and death. We developed a mathematical model incorporating the dual role of Beclin-1 to simulate Beclin-1-induced autophagy and apoptosis under varying ischemic...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-09-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225015317 |
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| Summary: | Summary: Beclin-1 plays a pivotal role in the interplay between autophagy and apoptosis in ischemic stroke, influencing both cell survival and death. We developed a mathematical model incorporating the dual role of Beclin-1 to simulate Beclin-1-induced autophagy and apoptosis under varying ischemic stress conditions. The model predicts a critical threshold of Beclin-1 expression, beyond which apoptosis is triggered, with this threshold decreasing as stress severity increases. To validate the model predictions, we conducted in vitro Beclin-1 overexpression and knockdown experiments under mild and severe oxygen-glucose deprivation (OGD) conditions and in vivo Beclin-1 knockdown in a photothrombotic mice model. The experiments demonstrated that Beclin-1 overexpression increases Caspase activation under severe OGD, while knockdown reduces it; the opposite effects were observed under mild OGD. Simulations suggest that modulating Beclin-1 expression could extend the therapeutic window for thrombolysis. Our approach provides insights into the dual roles of Beclin-1 and highlights potential strategies for neuroprotection. |
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| ISSN: | 2589-0042 |