Semaphorins 3A and 7A: potential immune and neuroregenerative targets in multiple sclerosis

Eixarch, Herena; Gutiérrez-Franco, Ana; Montalbán, Xavier; Espejo, Carmen

doi:10.1016/j.molmed.2013.01.003

Cited by 37 publications

(25 citation statements)

References 59 publications

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“…One of the most striking differences between MS converters and non-converters were observed for sema7A. Sema7A belongs to a family of membrane-bound and soluble proteins with roles in axonal guidance and immunomodulatory effects [ 9 ]. The decreased CSF levels of sema7A observed in MS converters may be related to its role as negative regulator of T-cell activation [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

Validation of semaphorin 7A and ala-β-his-dipeptidase as biomarkers associated with the conversion from clinically isolated syndrome to multiple sclerosis

Cantó

Tintoré

Villar

et al. 2014

J Neuroinflammation

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BackgroundIn a previous proteomics study using pooled cerebrospinal fluid (CSF) samples, we proposed apolipoprotein AI, apolipoprotein AIV, vitronectin, plasminogen, semaphorin 7A, and ala-β-his-dipeptidase as candidate biomarkers associated with the conversion to clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndromes (CIS). Here, we aimed to validate these results in individual CSF samples using alternative techniques.MethodsIn a first replication study, levels of apolipoproteins AI and AIV, vitronectin, and plasminogen were measured by ELISA in CSF and serum of 56 CIS patients (29 patients who converted to CDMS (MS converters) and 27 patients who remained with CIS during follow-up (MS non-converters)) and 26 controls with other neurological disorders. Semaphorin 7A and ala-β-his-dipeptidase levels were determined by selected reaction monitoring (SRM) in CSF of 36 patients (18 MS converters, 18 non-converters) and 20 controls. In a second replication study, apolipoprotein AI levels were measured by ELISA in CSF of 74 CIS patients (47 MS converters, 27 non-converters) and 50 individual controls, and levels of semaphorin 7A and ala-beta-his-dipeptidase were determined by SRM in 49 patients (24 MS converters, 25 non-converters) and 22 controls.ResultsCSF levels of apolipoprotein AI were increased (P = 0.043) and levels of semaphorin 7A and ala-β-his-dipeptidase decreased (P = 4.4 × 10−10 and P = 0.033 respectively) in MS converters compared to non-converters. No significant differences were found in serum levels for apolipoproteins AI and AIV, vitronectin, and plasminogen. Findings with semaphorin 7A and ala-β-his-dipeptidase were also validated in the second replication study, and CSF levels for these two proteins were again decreased in MS converters versus non-converters (P = 1.2 × 10−4 for semaphorin 7A; P = 3.7 × 10−8 for ala-β-his-dipeptidase). Conversely, apolipoprotein AI findings were not replicated and CSF levels for this protein did not significantly differ between groups. Furthermore, CSF semaphorin 7A levels were negatively associated with the number of T2 lesions at baseline and one-year follow-up.ConclusionsThese results validate previous findings for semaphorin 7A and ala-β-his-dipeptidase, and suggest that these proteins play a role as CSF biomarkers associated with the conversion to CDMS in CIS patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-014-0181-8) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Validation of semaphorin 7A and ala-β-his-dipeptidase as biomarkers associated with the conversion from clinically isolated syndrome to multiple sclerosis

Cantó

Tintoré

Villar

et al. 2014

J Neuroinflammation

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“…More recently they have been shown to play important roles in many physiologic and pathologic conditions such as cancer [65-67], multiple sclerosis [68], photoreceptor survival [25, 26], homeostasis of hormone system [69], and angiogenesis [27, 70, 71]. Therefore, recombinant semaphorin molecules have also been utilized for the treatments of various disease-related conditions in experimental models.…”

Section: Discussionmentioning

confidence: 99%

Neuroimmune semaphorin 4A as a drug and drug target for asthma

Mogie¹,

Shanks²,

Nkyimbeng-Takwi³

et al. 2013

International Immunopharmacology

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Neuroimmune semaphorin 4A (Sema4A) has been shown to play an important costimulatory role in T cell activation and regulation of Th1-mediated diseases such as multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE), and experimental autoimmune myocarditis (EAM). Sema4A has three functional receptors, Tim-2 expressed on CD4+ T cells, Th2 cells in particular, and Plexin B1 and D1 predominantly expressed on epithelial and endothelial cells, correspondingly. We recently showed that Sema4A has a complex expression pattern in lung tissue in a mouse model of asthma. We and others have shown that corresponding Plexin expression can be found on immune cells as well. Moreover, we demonstrated that Sema4A-deficient mice displayed significantly higher lung local and systemic allergic responses pointing to its critical regulatory role in the disease. To determine the utility of Sema4A as a novel immunotherapeutic, we introduced recombinant Sema4A protein to the allergen-sensitized WT and Sema4A−/− mice before allergen challenge. We observed significant reductions in the allergic inflammatory lung response in Sema4A-treated mice as judged by tissue inflammation including eosinophilia and mucus production. Furthermore, we demonstrated that in vivo administration of anti-Tim2 Ab led to a substantial upregulation of allergic inflammation in WT mouse lungs. These data highlight the potential to develop Sema4A as a new therapeutic for allergic airway disease.

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“…During injury, semaphorins, especially semaphorin3A are expressed by glial scar associated meningeal cells and are responsible for growth inhibition. Injury to the dorsal columns of the spinal cord induced strong expression of semaphorin3A mRNA in fibroblasts associated with the glial scar, and semaphorin3A receptors were present on injured dorsal column axons; dorsal column axons fail to penetrate the semaphorin3Aexpressing scar tissue (4).…”

Section: Intrinsic Factorsmentioning

confidence: 99%

Stem Cells for Neuro-regeneration: State of the Art

Wagih¹,

Elhawary²,

Ellessy³

et al. 2015

BIO

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Neuroregeneration (NR) is a long-sought medical dream which has intrigued vast research in the past decades. A traditional physiologic dogma that central nervous system does not regenerate has been strongly challenged in the recent years since the advent of the stem cell era. Stem cell research in the regenerative field passes through three main stages. The first stage is the in-vitro experiments which studies the exact molecular and cellular mechanisms underlying stem cell-mediated NR. The second stage is the application of these data in experimental animal settings to provide "proof of concept" of stem cell therapy in animal models. The final step is the translation of these data in pilot clinical trials. In this review, we will try to gather the different data of stem cell-mediated NR from various experimental and clinical researches.

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Semaphorins 3A and 7A: potential immune and neuroregenerative targets in multiple sclerosis

Cited by 37 publications

References 59 publications

Validation of semaphorin 7A and ala-β-his-dipeptidase as biomarkers associated with the conversion from clinically isolated syndrome to multiple sclerosis

Validation of semaphorin 7A and ala-β-his-dipeptidase as biomarkers associated with the conversion from clinically isolated syndrome to multiple sclerosis

Neuroimmune semaphorin 4A as a drug and drug target for asthma

Stem Cells for Neuro-regeneration: State of the Art

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