PI3K/AKT signaling and neuroprotection in ischemic stroke: molecular mechanisms and therapeutic perspectives

It has been reported that the PI3K/AKT signaling pathway plays a key role in the pathogenesis of ischemic stroke. As a result, the development of drugs targeting the PI3K/AKT signaling pathway has attracted increasing attention from researchers. This article reviews the pathological mechanisms and a...

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Main Authors: Tianlong Liu, Xiaolin Li, Xiaowei Zhou, Wei Chen, Aidong Wen, Minna Liu, Yi Ding
Format: Article
Language:English
Published: Wolters Kluwer Medknow Publications 2025-10-01
Series:Neural Regeneration Research
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Online Access:https://journals.lww.com/10.4103/NRR.NRR-D-24-00568
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author Tianlong Liu
Xiaolin Li
Xiaowei Zhou
Wei Chen
Aidong Wen
Minna Liu
Yi Ding
author_facet Tianlong Liu
Xiaolin Li
Xiaowei Zhou
Wei Chen
Aidong Wen
Minna Liu
Yi Ding
author_sort Tianlong Liu
collection DOAJ
description It has been reported that the PI3K/AKT signaling pathway plays a key role in the pathogenesis of ischemic stroke. As a result, the development of drugs targeting the PI3K/AKT signaling pathway has attracted increasing attention from researchers. This article reviews the pathological mechanisms and advancements in research related to the signaling pathways in ischemic stroke, with a focus on the PI3K/AKT signaling pathway. The key findings include the following: (1) The complex pathological mechanisms of ischemic stroke can be categorized into five major types: excitatory amino acid toxicity, Ca2+ overload, inflammatory response, oxidative stress, and apoptosis. (2) The PI3K/AKT-mediated signaling pathway is closely associated with the occurrence and progression of ischemic stroke, which primarily involves the NF-κB, NRF2, BCL-2, mTOR, and endothelial NOS signaling pathways. (3) Natural products, including flavonoids, quinones, alkaloids, phenylpropanoids, phenols, terpenoids, and iridoids, show great potential as candidate substances for the development of innovative anti-stroke medications. (4) Recently, novel therapeutic techniques, such as electroacupuncture and mesenchymal stem cell therapy, have demonstrated the potential to improve stroke outcomes by activating the PI3K/AKT signaling pathway, providing new possibilities for the treatment and rehabilitation of patients with ischemic stroke. Future investigations should focus on the direct regulatory mechanisms of drugs targeting the PI3K/AKT signaling pathway and their clinical translation to develop innovative treatment strategies for ischemic stroke.
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publishDate 2025-10-01
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spelling doaj-art-24c9d82b8efc45588d247c504d11a54c2024-12-09T09:33:30ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53741876-79582025-10-0120102758277510.4103/NRR.NRR-D-24-00568PI3K/AKT signaling and neuroprotection in ischemic stroke: molecular mechanisms and therapeutic perspectivesTianlong LiuXiaolin LiXiaowei ZhouWei ChenAidong WenMinna LiuYi DingIt has been reported that the PI3K/AKT signaling pathway plays a key role in the pathogenesis of ischemic stroke. As a result, the development of drugs targeting the PI3K/AKT signaling pathway has attracted increasing attention from researchers. This article reviews the pathological mechanisms and advancements in research related to the signaling pathways in ischemic stroke, with a focus on the PI3K/AKT signaling pathway. The key findings include the following: (1) The complex pathological mechanisms of ischemic stroke can be categorized into five major types: excitatory amino acid toxicity, Ca2+ overload, inflammatory response, oxidative stress, and apoptosis. (2) The PI3K/AKT-mediated signaling pathway is closely associated with the occurrence and progression of ischemic stroke, which primarily involves the NF-κB, NRF2, BCL-2, mTOR, and endothelial NOS signaling pathways. (3) Natural products, including flavonoids, quinones, alkaloids, phenylpropanoids, phenols, terpenoids, and iridoids, show great potential as candidate substances for the development of innovative anti-stroke medications. (4) Recently, novel therapeutic techniques, such as electroacupuncture and mesenchymal stem cell therapy, have demonstrated the potential to improve stroke outcomes by activating the PI3K/AKT signaling pathway, providing new possibilities for the treatment and rehabilitation of patients with ischemic stroke. Future investigations should focus on the direct regulatory mechanisms of drugs targeting the PI3K/AKT signaling pathway and their clinical translation to develop innovative treatment strategies for ischemic stroke.https://journals.lww.com/10.4103/NRR.NRR-D-24-00568apoptosisautophagyinflammationischemic strokeneuroprotectionoxidative stresspathogenesisphosphatidylinositol 3-kinaseprotein kinase btherapeutics
spellingShingle Tianlong Liu
Xiaolin Li
Xiaowei Zhou
Wei Chen
Aidong Wen
Minna Liu
Yi Ding
PI3K/AKT signaling and neuroprotection in ischemic stroke: molecular mechanisms and therapeutic perspectives
Neural Regeneration Research
apoptosis
autophagy
inflammation
ischemic stroke
neuroprotection
oxidative stress
pathogenesis
phosphatidylinositol 3-kinase
protein kinase b
therapeutics
title PI3K/AKT signaling and neuroprotection in ischemic stroke: molecular mechanisms and therapeutic perspectives
title_full PI3K/AKT signaling and neuroprotection in ischemic stroke: molecular mechanisms and therapeutic perspectives
title_fullStr PI3K/AKT signaling and neuroprotection in ischemic stroke: molecular mechanisms and therapeutic perspectives
title_full_unstemmed PI3K/AKT signaling and neuroprotection in ischemic stroke: molecular mechanisms and therapeutic perspectives
title_short PI3K/AKT signaling and neuroprotection in ischemic stroke: molecular mechanisms and therapeutic perspectives
title_sort pi3k akt signaling and neuroprotection in ischemic stroke molecular mechanisms and therapeutic perspectives
topic apoptosis
autophagy
inflammation
ischemic stroke
neuroprotection
oxidative stress
pathogenesis
phosphatidylinositol 3-kinase
protein kinase b
therapeutics
url https://journals.lww.com/10.4103/NRR.NRR-D-24-00568
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