The Demonstration of an Aqp4/Tgf-Beta 1 Pathway in Murine Astrocytes Holds Implications for Both Neuromyelitis Optica and Progressive Multiple Sclerosis

Nataf, Serge

doi:10.3390/ijms21031035

Cited by 5 publications

(2 citation statements)

References 35 publications

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“…Alternatively, these data may reflect differences in the microenvironment upon demyelination. Indeed, demyelination changes the expression of several growth factors, including fibroblast growth factor and transforming growth factor b1 (Huang and Dreyfus, 2016), which can regulate Gli2 expression (Brewster et al, 2000;Javelaud et al, 2011) and astrocyte generation (Nataf, 2020;Savchenko et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Relative Levels of Gli1 and Gli2 Determine the Response of Ventral Neural Stem Cells to Demyelination

et al. 2020

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Enhancing repair of myelin is an important therapeutic goal in many neurological disorders characterized by demyelination. In the healthy adult brain, ventral neural stem cells (vNSCs) in the subventricular zone, marked by GLI1 expression, do not generate oligodendrocytes. However, in response to demyelination, their progeny are recruited to lesions where they differentiate into oligodendrocytes and ablation of GLI1 further enhances remyelination. GLI1 and GLI2 are closely related transcriptional activators but the role of GLI2 in remyelination by vNSCs is not clear. Here, we show that genetic ablation of Gli1 in vNSCs increases GLI2 expression and combined loss of both transcription factors decreases the recruitment and differentiation of their progeny in demyelinated lesions. These results indicate that GLI1 and GLI2 have distinct, non-redundant functions in vNSCs and their relative levels play an essential role in the response to demyelination.

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Section: Discussionmentioning

confidence: 99%

Relative Levels of Gli1 and Gli2 Determine the Response of Ventral Neural Stem Cells to Demyelination

et al. 2020

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“…In 2004, it was found that the serum from patients with NMO contains autoantibodies directed against the astrocytic protein aquaporin 4 (AQP4) [59]. More recently, it was suggested that these antibodies can interfere with the systemic and intra-cerebral synthesis of transforming growth factor β1 (TGF-β1), thus abolishing an important anti-inflammatory response [60].…”

Section: Discussionmentioning

confidence: 99%

Toxic effects on astrocytes of extracellular vesicles from CSF of multiple sclerosis patients: a pilot in vitro study

Ragonese

Liegro

Schiera

et al. 2020

pjp

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Multiple sclerosis (MS) is an autoimmune and degenerative disorder of the central nervous system (CNS) that causes a progressive loss of motor and cognitive performances. Moreover, since the earlier phases, axonal loss as well as neuronal degeneration and a failure of oligodendrocytes to promote myelin repair have been demonstrated. In previous studies, it has been shown that the treatment of rat neuronal primary cultures with serum from MS patients can be toxic for neurons. Here we report a pilot investigation showing that CSF from patients contains extracellular vesicles (EVs) able to induce cell death in rat cultured astrocytes. Although these data are still preliminary, they suggest at least two notable considerations: i) EVs can be instrumental to pathology, and their concentration in CSF might be proportional to MS severity; ii) astrocytes can be part of the degenerative process. As a consequence, we propose that cultured astrocytes can be used as a model to study the toxicity of EVs from patients affected by MS at different stages. In addition, we suggest that EVs and their cargoes might be used as biomarkers of MS severity.

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Transforming growth factor β (TGF-β) pathway in the immunopathogenesis of multiple sclerosis (MS); molecular approaches

2023

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Multiple sclerosis (MS) is an acute demyelinating disease with an autoimmune nature, followed by gradual neurodegeneration and enervating scar formation. Dysregulated immune response is an important dilemma contributing to the pathogenesis of MS. The role of chemokines and cytokines, such as transforming growth factor-β (TGF-β), have been recently highlighted regarding their altered expressions in MS. TGF-β has three isoforms, TGF-β1, TGF-β2, and TGF-β3, that are structurally similar; however, they can show different functions. All three isoforms are known to induce immune tolerance by modifying Foxp3 + regulatory T cells. Nevertheless, there are controversial reports concerning the role of TGF-β1 and 2 in the progression of scar formation in MS, while these proteins are also known to improve oligodendrocyte differentiation and have shown neuroprotective behavior, two cellular processes that suppress the pathogenesis of MS. TGF-β3 shares the same properties but is less likely to contribute to scar formation and its direct role in MS remains elusive. To develop novel neuroimmunological treatment strategies for MS, the optimal strategy could be the one that causes immune suppression, induces neurogenesis, stimulates remyelination, and prevents excessive scar formation. Therefore, regarding its immunological properties, TGF-β could be an appropriate candidate for this; however, contradictory results of previous studies have questioned its role and therapeutic potential in MS. In this review article, we provide an overview of the immunopathogenesis of MS, the role of TGF-β in this process, related clinical and animal studies, and the treatment potential of TGF-β in MS by emphasizing the role of different TGF-β isoforms.

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The Demonstration of an Aqp4/Tgf-Beta 1 Pathway in Murine Astrocytes Holds Implications for Both Neuromyelitis Optica and Progressive Multiple Sclerosis

Cited by 5 publications

References 35 publications

Relative Levels of Gli1 and Gli2 Determine the Response of Ventral Neural Stem Cells to Demyelination

Relative Levels of Gli1 and Gli2 Determine the Response of Ventral Neural Stem Cells to Demyelination

Toxic effects on astrocytes of extracellular vesicles from CSF of multiple sclerosis patients: a pilot in vitro study

Transforming growth factor β (TGF-β) pathway in the immunopathogenesis of multiple sclerosis (MS); molecular approaches

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