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The complex steps leading to the central nervous system (CNS) inflammation and the progress to neuroinflammatory and neurodegenerative disorders have opened up new research and intervention avenues. This review focuses on the therapeutic targeting of the VLA-4 integrin to discuss the clear-cut effect on immune cell trafficking into brain tissues. Besides, we explore the possibility that blocking VLA-4 may have a relevant impact on nonmigratory activities of immune cells, such as antigen presentation and T-cell differentiation, during the neuroinflammatory process. Lastly, the recent refinement of computational techniques is highlighted as a way to increase specificity and to reduce the detrimental side effects of VLA-4 immunotherapies aiming at developing better clinical interventions.
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http://dx.doi.org/10.1159/000518721 | DOI Listing |
Neurotherapeutics
September 2025
Department of Neurology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong 510280, PR China. Electronic address:
Mitochondrial dysfunction and lipid metabolic disturbance may promote pathologic α-synuclein (α-syn) aggregation, accelerating the progression of Parkinson's disease (PD). Whether extracellular matrices are associated with those pathological mechanisms in PD remains elusive. Here, we aimed to identify if cellular fibronectin (cFn), a component of extracellular matrices, contributes to α-syn abnormality via inducing mitochondrial energy depletion or disrupting lipid homeostasis.
View Article and Find Full Text PDFTherapeutic T-cell engineering from human hematopoietic stem cells (HSCs) focuses on recapitulating notch1-signaling and α4β1-integrin-mediated adhesion within the thymic niche with supportive stromal cell feeder-layers or surface-immobilized recombinant protein-based engineered thymic niches (ETNs). The relevant Notch1-DLL-4 and α4β1-integrin-VCAM-1 interactions are known to respond to mechanical forces that regulate their bond dissociation behaviors and downstream signal transduction, yet manipulating the mechanosensitive features of these key receptor-ligand interactions in thymopoiesis has been largely ignored in current ETN designs. Here, we demonstrate that human T-cell development from cord blood-derived CD34 HSCs is regulated via molecular cooperativity in notch1 and integrin-mediated mechanotransduction.
View Article and Find Full Text PDFBioconjug Chem
August 2025
Molecular Imaging and Theranostics Center, University of Missouri, Columbia, Missouri 65211, United States.
The transmembrane integrin, very late antigen-4 (VLA-4), which is a critical integrin involved in promoting tumor progression, angiogenesis, and metastasis, is overexpressed in metastatic melanoma. The peptidomimetic LLP2A has a high binding affinity to VLA-4 and is used as a radiopharmaceutical targeting agent for imaging and therapy. Previous studies demonstrated that the albumin-binding compound, [Lu]Lu-DOTAGA-pIBA-PEG-LLP2A, significantly improved tumor retention and blood circulation time but resulted in lower tumor-to-nontumor tissue ratios compared to the nonalbumin-binding compound, [Lu]Lu-DOTAGA-PEG-LLP2A.
View Article and Find Full Text PDFJ Surg Res
September 2025
Department of Surgery, University of Cincinnati, Cincinnati, Ohio. Electronic address:
Introduction: Endotheliopathy is well studied in chronic kidney disease, brought on by the chronic stressors of proinflammatory cytokines and reactive oxygen species. However, the endothelial response to renal transplantation has not been well investigated. This study aimed to evaluate circulating biomarkers of endothelial injury acutely after renal transplantation.
View Article and Find Full Text PDFEur J Med Chem
November 2025
Department of Chemistry "Giacomo Ciamician" University of Bologna, Via Piero Gobetti, 85, 40129, Bologna, Italy. Electronic address:
The immune system depends on integrins for adhesion and migration during leukocyte trafficking and for intracellular signalling. There is a causal relationship between dysregulation of integrin expression and the onset of pathological conditions, such as autoimmune diseases, inflammation, cancer, and infections. Therefore, integrins, such as αβ, are considered important therapeutic targets.
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