Targeting PI3K/Akt in Cerebral Ischemia Reperfusion Injury Alleviation: From Signaling Networks to Targeted Therapy.
Mol Neurobiol
; 61(10): 7930-7949, 2024 Oct.
Article
em En
| MEDLINE
| ID: mdl-38441860
ABSTRACT
Ischemia/reperfusion (I/R) injury is a pathological event that results in reperfusion due to low blood flow to an organ. Cerebral ischemia is a common cerebrovascular disease with high mortality, and reperfusion is the current standard intervention. However, reperfusion may further induce cellular damage and dysfunction known as cerebral ischemia/reperfusion injury (CIRI). Currently, strategies for the clinical management of CIRI are limited, necessitating the exploration of novel and efficacious treatment modalities for the benefit of patients. PI3K/Akt signaling pathway is an important cellular process associated with the disease. Stimulation of the PI3K/Akt pathway enhances I/R injury in multiple organs such as heart, brain, lung, and liver. It stands as a pivotal signaling pathway crucial for diminishing cerebral infarction size and safeguarding the functionality of brain tissue after CIRI. During CIRI, activation of the PI3K/Akt pathway exhibits a protective effect on CIRI. Furthermore, activation of the PI3K/Akt pathway has the potential to augment the activity of antioxidant enzymes, resulting in a decrease in reactive oxygen species (ROS) and the associated oxidative stress. Meanwhile, PI3K/Akt plays a neuroprotective role by inhibiting inflammatory responses and apoptosis. For example, PI3K/Akt interacts with NF-κB, Nrf2, and MAPK signaling pathways to mitigate CIRI. This article is aimed to explore the pivotal role and underlying mechanism of PI3K/Akt in ameliorating CIRI and investigate the influence of ischemic preconditioning and post-processing, as well as the impact of pertinent drugs or activators targeting the PI3K/Akt pathway on CIRI. The primary objective is to furnish compelling evidence supporting the activation of PI3K/Akt in the context of CIRI, elucidating its mechanistic intricacies. By doing so, the paper aims to underscore the critical contribution of PI3K/Akt in mitigating CIRI, providing a theoretical foundation for considering the PI3K/Akt pathway as a viable target for CIRI treatment.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Traumatismo por Reperfusão
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Transdução de Sinais
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Isquemia Encefálica
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Fosfatidilinositol 3-Quinases
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Proteínas Proto-Oncogênicas c-akt
Limite:
Animals
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Humans
Idioma:
En
Revista:
Mol Neurobiol
Assunto da revista:
BIOLOGIA MOLECULAR
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NEUROLOGIA
Ano de publicação:
2024
Tipo de documento:
Article