Regulation of Blood-Brain Barrier Permeability via JNK Signaling Pathway: Mechanisms and Potential Therapeutic Strategies for Ischemic Stroke, Alzheimer's Disease and Brain Tumors.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, c1995-

Blood-Brain Barrier*/metabolism ; Blood-Brain Barrier*/drug effects ; Blood-Brain Barrier*/pathology ; Alzheimer Disease*/metabolism ; Alzheimer Disease*/drug therapy ; Alzheimer Disease*/pathology ; MAP Kinase Signaling System*/drug effects ; Brain Neoplasms*/metabolism ; Brain Neoplasms*/drug therapy ; Brain Neoplasms*/pathology ; Ischemic Stroke*/metabolism ; Ischemic Stroke*/drug therapy ; Ischemic Stroke*/pathology ; JNK Mitogen-Activated Protein Kinases*/metabolism; Humans ; Animals ; Oxidative Stress ; Permeability

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.

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24-15-00334 Russian Science Foundation

Keywords: Alzheimer’s disease; JNK inhibitor; JNK pathway; blood–brain barrier; brain tumor; c-Jun N-terminal kinase (JNK); ischemia/reperfusion

EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)

Date Created: 20250613 Date Completed: 20250613 Latest Revision: 20250617

20250617

PMC12156458

10.3390/molecules30112353

40509244