Celastrol Ameliorates Neuronal Mitochondrial Dysfunction Induced by Intracerebral Hemorrhage via Targeting cAMP‐Activated Exchange Protein‐1
Abstract: Mitochondrial dysfunction contributes to the development of secondary brain injury (SBI) following intracerebral hemorrhage (ICH) and represents a promising therapeutic target. Celastrol, the primary active component of Tripterygium wilfordii, is a natural product that exhibits mitochondrial and neuronal protection in various cell types. This study aims to investigate the neuroprotective effects of celastrol against ICH‐induced SBI and explore its underlying mechanisms. Celastrol improves neurobehavioral and cognitive abilities in mice with autologous blood‐induced ICH, reduces neuronal death in vivo and in vitro, and promotes mitochondrial function recovery in neurons. Single‐cell nuclear sequencing reveals that the cyclic adenosine monophosphate (cAMP)/cAMP‐activated exchange protein‐1 (EPAC‐1) signaling pathways are impacted by celastrol. Celastrol binds to cNMP (a domain of EPAC‐1) to inhibit its interaction with voltage‐dependent anion‐selective channel protein 1 (VDAC1) and blocks the opening of mitochondrial permeability transition pores. After neuron‐specific knockout of EPAC1, the neuroprotective effects of celastrol are diminished. In summary, this study demonstrates that celastrol, through its interaction with EPAC‐1, ameliorates mitochondrial dysfunction in neurons, thus potentially improving SBI induced by ICH. These findings suggest that targeting EPAC‐1 with celastrol can be a promising therapeutic approach for treating ICH‐induced SBI.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Celastrol Ameliorates Neuronal Mitochondrial Dysfunction Induced by Intracerebral Hemorrhage via Targeting cAMP‐Activated Exchange Protein‐1 ; day:14 ; month:03 ; year:2024 ; extent:21
Advanced science ; (14.03.2024) (gesamt 21)
- Creator
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Li, Xiang
Liu, Wen
Jiang, Guannan
Lian, Jinrong
Zhong, Yi
Zhou, Jialei
Li, Haiying
Xu, Xingshun
Liu, Yaobo
Cao, Cong
Tao, Jin
Cheng, Jian
Zhang, John H.
Chen, Gang
- DOI
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10.1002/advs.202307556
- URN
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urn:nbn:de:101:1-2024031413334242622862
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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14.08.2025, 10:56 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Li, Xiang
- Liu, Wen
- Jiang, Guannan
- Lian, Jinrong
- Zhong, Yi
- Zhou, Jialei
- Li, Haiying
- Xu, Xingshun
- Liu, Yaobo
- Cao, Cong
- Tao, Jin
- Cheng, Jian
- Zhang, John H.
- Chen, Gang
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