Regulation of Blood–Brain Barrier Permeability via JNK Signaling Pathway: Mechanisms and Potential Therapeutic Strategies for Ischemic Stroke, Alzheimer’s Disease and Brain Tumors
Disruption of the blood–brain barrier (BBB) accompanies many brain diseases, including stroke, neurodegenerative diseases, and brain tumors, leading to swelling, increased neuroinflammation, and neuronal death. In recent years, it has become clear that the c-Jun N-terminal kinase (JNK) signaling pat...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-05-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/30/11/2353 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849331208407744512 |
|---|---|
| author | Mark B. Plotnikov Anna M. Anishchenko Andrei I. Khlebnikov Igor A. Schepetkin |
| author_facet | Mark B. Plotnikov Anna M. Anishchenko Andrei I. Khlebnikov Igor A. Schepetkin |
| author_sort | Mark B. Plotnikov |
| collection | DOAJ |
| description | Disruption of the blood–brain barrier (BBB) accompanies many brain diseases, including stroke, neurodegenerative diseases, and brain tumors, leading to swelling, increased neuroinflammation, and neuronal death. In recent years, it has become clear that the c-Jun N-terminal kinase (JNK) signaling pathway is involved in disruption of the structural integrity of the BBB. Activation of the JNK signaling pathway has a negative effect on the functioning of the cellular elements of the neurovascular unit that form the BBB. The aim of this review is to assess the role of the JNK signaling pathway in the disruption of the structural integrity of the BBB in animal models of stroke (MCAO/R, middle cerebral artery occlusion with reperfusion), Alzheimer’s disease, and brain tumors and to analyze the effects of compounds of various natures that directly or indirectly affect the activity of the JNK signaling pathway. These compounds can reduce damage to the BBB and brain edema, reduce neuroinflammation and oxidative stress, reduce the expression of proapoptotic factors, and increase the expression of tight junction proteins. Certain compounds mitigate BBB dysfunction, being promising candidates for neuroprotective therapies. These agents exert their effects, in part, through inhibition of the c-Jun N-terminal kinase (JNK) signaling pathway, a mechanism linked to reduced neuronal damage and improved BBB integrity. |
| format | Article |
| id | doaj-art-1dc5a1e47e7d44d7b6f7b0c237ec79be |
| institution | Kabale University |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj-art-1dc5a1e47e7d44d7b6f7b0c237ec79be2025-08-20T03:46:42ZengMDPI AGMolecules1420-30492025-05-013011235310.3390/molecules30112353Regulation of Blood–Brain Barrier Permeability via JNK Signaling Pathway: Mechanisms and Potential Therapeutic Strategies for Ischemic Stroke, Alzheimer’s Disease and Brain TumorsMark B. Plotnikov0Anna M. Anishchenko1Andrei I. Khlebnikov2Igor A. Schepetkin3Department of Pharmacology, Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk 634028, RussiaDepartment of Pharmacology, Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk 634028, RussiaKizhner Research Center, National Research Tomsk Polytechnic University, Tomsk 634050, RussiaDepartment of Microbiology and Cell Biology, Montana State University, Bozeman, MT 59717, USADisruption of the blood–brain barrier (BBB) accompanies many brain diseases, including stroke, neurodegenerative diseases, and brain tumors, leading to swelling, increased neuroinflammation, and neuronal death. In recent years, it has become clear that the c-Jun N-terminal kinase (JNK) signaling pathway is involved in disruption of the structural integrity of the BBB. Activation of the JNK signaling pathway has a negative effect on the functioning of the cellular elements of the neurovascular unit that form the BBB. The aim of this review is to assess the role of the JNK signaling pathway in the disruption of the structural integrity of the BBB in animal models of stroke (MCAO/R, middle cerebral artery occlusion with reperfusion), Alzheimer’s disease, and brain tumors and to analyze the effects of compounds of various natures that directly or indirectly affect the activity of the JNK signaling pathway. These compounds can reduce damage to the BBB and brain edema, reduce neuroinflammation and oxidative stress, reduce the expression of proapoptotic factors, and increase the expression of tight junction proteins. Certain compounds mitigate BBB dysfunction, being promising candidates for neuroprotective therapies. These agents exert their effects, in part, through inhibition of the c-Jun N-terminal kinase (JNK) signaling pathway, a mechanism linked to reduced neuronal damage and improved BBB integrity.https://www.mdpi.com/1420-3049/30/11/2353Alzheimer’s diseaseblood–brain barrierbrain tumorischemia/reperfusionc-Jun N-terminal kinase (JNK)JNK pathway |
| spellingShingle | Mark B. Plotnikov Anna M. Anishchenko Andrei I. Khlebnikov Igor A. Schepetkin Regulation of Blood–Brain Barrier Permeability via JNK Signaling Pathway: Mechanisms and Potential Therapeutic Strategies for Ischemic Stroke, Alzheimer’s Disease and Brain Tumors Molecules Alzheimer’s disease blood–brain barrier brain tumor ischemia/reperfusion c-Jun N-terminal kinase (JNK) JNK pathway |
| title | Regulation of Blood–Brain Barrier Permeability via JNK Signaling Pathway: Mechanisms and Potential Therapeutic Strategies for Ischemic Stroke, Alzheimer’s Disease and Brain Tumors |
| title_full | Regulation of Blood–Brain Barrier Permeability via JNK Signaling Pathway: Mechanisms and Potential Therapeutic Strategies for Ischemic Stroke, Alzheimer’s Disease and Brain Tumors |
| title_fullStr | Regulation of Blood–Brain Barrier Permeability via JNK Signaling Pathway: Mechanisms and Potential Therapeutic Strategies for Ischemic Stroke, Alzheimer’s Disease and Brain Tumors |
| title_full_unstemmed | Regulation of Blood–Brain Barrier Permeability via JNK Signaling Pathway: Mechanisms and Potential Therapeutic Strategies for Ischemic Stroke, Alzheimer’s Disease and Brain Tumors |
| title_short | Regulation of Blood–Brain Barrier Permeability via JNK Signaling Pathway: Mechanisms and Potential Therapeutic Strategies for Ischemic Stroke, Alzheimer’s Disease and Brain Tumors |
| title_sort | regulation of blood brain barrier permeability via jnk signaling pathway mechanisms and potential therapeutic strategies for ischemic stroke alzheimer s disease and brain tumors |
| topic | Alzheimer’s disease blood–brain barrier brain tumor ischemia/reperfusion c-Jun N-terminal kinase (JNK) JNK pathway |
| url | https://www.mdpi.com/1420-3049/30/11/2353 |
| work_keys_str_mv | AT markbplotnikov regulationofbloodbrainbarrierpermeabilityviajnksignalingpathwaymechanismsandpotentialtherapeuticstrategiesforischemicstrokealzheimersdiseaseandbraintumors AT annamanishchenko regulationofbloodbrainbarrierpermeabilityviajnksignalingpathwaymechanismsandpotentialtherapeuticstrategiesforischemicstrokealzheimersdiseaseandbraintumors AT andreiikhlebnikov regulationofbloodbrainbarrierpermeabilityviajnksignalingpathwaymechanismsandpotentialtherapeuticstrategiesforischemicstrokealzheimersdiseaseandbraintumors AT igoraschepetkin regulationofbloodbrainbarrierpermeabilityviajnksignalingpathwaymechanismsandpotentialtherapeuticstrategiesforischemicstrokealzheimersdiseaseandbraintumors |