Selectins and Their Ligands as Potential Immunotherapeutic Targets in Neurological Diseases

Angiari, Stefano; Constantin, Gabriela

doi:10.2217/imt.13.122

Cited by 14 publications

(15 citation statements)

References 137 publications

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“…There are three subsets of L‐selectin (81‐kDa), E‐selectin (115‐kDa) and P‐selectin (140‐kDa); L‐selectin is expressed on lymphocytes, and the E‐ and P‐selectin are expressed on activated endothelial cells. These selectins bind to highly glycosylated ligands expressed on the surface of lymphocytes and endothelial cells …”

Section: Selectinsmentioning

confidence: 99%

“…These selectins bind to highly glycosylated ligands expressed on the surface of lymphocytes and endothelial cells. 8 L-selectin is required for the localization of lymphocytes at inflammatory sites, and E-and P-selectin is considered to play complementary roles in regulating leukocyte-endothelial interactions. Under normal conditions, E-selectin is expressed in meningeal vessels, and P-selectin is preferentially expressed in meningeal and choroidal vessels in the brain, suggesting the participation in immunosurveillance in the CNS.…”

Section: Selectinsmentioning

confidence: 99%

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Blood–brain barrier: A novel therapeutic target in multiple sclerosis

Kuwahara

Nishina

Yokota

2015

Clinical & Exp Neuroim

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Multiple sclerosis is an autoimmune inflammatory disorder of the central nervous system, and the entrance of pathogenic lymphocytes from blood circulation into the brain across the blood–brain barrier (BBB) is accepted as the initial step of pathogenesis. The migration of lymphocytes across the BBB is mediated by their sequential interactions with the brain microvascular endothelial cells, the central component of the BBB, including rolling (loose attachment), adhesion (firm attachment), crawling and transmigration. There are a variety of cell adhesion molecules that are expressed on brain microvascular endothelial cells and are involved in this process. The selectins are assumed to be associated with the rolling of lymphocytes. Vascular cell adhesion molecule‐1 contributes to the adhesion of lymphocytes by binding to very late antigen‐4 on their surface after the stimulation by cytokines. Intercellular adhesion molecule‐1 acts for the adhesion as well and the subsequent crawling of lymphocytes by binding to leukocyte function‐associated antigen‐1 on their surface. Activated leukocyte cell adhesion molecule, melanoma cell adhesion molecule, platelet endothelial cell adhesion molecule‐1, nerve injury‐induced protein‐1 and vascular adhesion protein‐1 are also considered to influence the migratory process of lymphocytes across the BBB, although the detailed mechanisms are not elucidated. Here we review the pathophysiology of multiple sclerosis at the BBB to present a possible molecular targeted therapy in the future, especially focused on the molecules expressing at the brain microvascular endothelial cells.

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Section: Selectinsmentioning

confidence: 99%

Section: Selectinsmentioning

confidence: 99%

Blood–brain barrier: A novel therapeutic target in multiple sclerosis

Kuwahara

Nishina

Yokota

2015

Clinical & Exp Neuroim

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“…YSPLS is being evaluated in preclinical epilepsy models in collaboration with Constantin and colleagues. 86 Immunosuppressants In epileptogenesis, cyclosporine A, FK-506 (also known as Tacrolimus), and rapamycin have been used. 87 Among their various mechanisms of action, one of the best characterized is the inhibition of T-lymphocyte activation.…”

Section: Further Strategies Against Convulsive Inflammation Antibody mentioning

confidence: 99%

Targeting inflammation as a therapeutic strategy for drug-resistant epilepsies

Vitaliti

Pavone

Mahmood

et al. 2014

Human Vaccines & Immunotherapeutics

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An increasing body of literature data suggests that inflammation, and in particular neuroinflammation, is involved in the pathophysiology of particular forms of epilepsy and convulsive disorders. Animal models have been used to identify inflammatory triggers in epileptogenesis and inflammation has recently been shown to enhance seizures. For example, pharmacological blockade of the IL-1beta/IL-1 receptor type 1 axis during epileptogenesis has been demonstrated to provide neuroprotection in temporal lobe epilepsy. Furthermore, experimental models have suggested that neural damage and the onset of spontaneous recurrent seizures are modulated via complex interactions between innate and adaptive immunity. However, it has also been suggested that inflammation can occur as a result of epilepsy, since animal models have also shown that seizure activity can induce neuroinflammation, and that recurrent seizures maintain chronic inflammation, thereby perpetuating seizures. On the basis of these observations, it has been suggested that immune-mediated therapeutic strategies may be beneficial for treating some drug resistant epilepsies with an underlying demonstrable inflammatory process. Although the potential mechanisms of immunotherapeutic strategies in drug-resistant seizures have been extensively discussed, evidence on the efficacy of such therapy is limited. However, recent research efforts have been directed toward utilizing the potential therapeutic benefits of anti-inflammatory agents in neurological disease and these are now considered prime candidates in the ongoing search for novel anti-epileptic drugs. The objective of our review is to highlight the immunological features of the pathogenesis of seizures and to analyze possible immunotherapeutic approaches for drug resistant epilepsies that can alter the immune-mediated pathogenesis.

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“…Accordingly, PSGL-1 deficiency or inhibition has a severe impact on leukocyte trafficking to target tissues during inflammatory diseases [7,8,114]. By contrast, TIM-1 acts specifically as a P-selectin ligand in vivo, suggesting that TIM-1 inhibition could reduce T cell trafficking during inflammatory diseases in which P-selectin plays a predominant role [9].…”

Section: Reviewmentioning

confidence: 99%

“…Th1 cells produce interferon gamma (IFNg), tumor necrosis factor alpha/beta (TNFa/b), and IL-2, whereas the effector cytokines associated with Th17 cells are IL-17A, IL-17F, IL-21, and IL- 22. generation of inflammatory responses. Anti-selectin therapies have, therefore, been developed for the treatment of human inflammatory and autoimmune pathologies [1,7,8].…”

mentioning

confidence: 99%