Outline

  • 1. Introduction
  • 2. Jak-Stat Signalling Pathway
  • 3. Jak-Stat Pathway Activation in Response to Sci
  • 4. Role of Jak-Stat in Axon Regeneration and Collateral Sprouting
  • 5. Role of Jak-Stat in Local Neuron Response
  • 6. Role of Jak-Stat in Glial Response
  • 7. Role of Jak-Stat in the Inflammatory Response
  • 8. Conclusion and Clinical Implications
  • Acknowledgments

رئوس مطالب

  • چکیده
  • 1. مقدمه
  • 2. مسیر سیگنال دهی JAK-STAT
  • 3. فعال سازی مسیر JAK در پاسخ به SCI
  • 3.1.بیان سیتوکین در پاسخ به SCI
  • 3.2. سیگنال دهی JAK-STAT در پاسخ به SCI
  • 4. نقش JAK-STAT در بازسازی آکسون و جوانه زنی کلترال
  • 4.1. نقش مسیر JAK-STAT در بازسازی آکسون در SCI و دیگر مدل های آسیب عصبی
  • 4.1.1. بازسازی آکسون پس از گانگلیون ریشه پشتی یا آکسوتومی عصب بینایی
  • 4.1.2. بازسازی آکسون پس از آسیب دیدگی نخاعی
  • 4.2. نقش JAK-STAT در بازسازی مدار به وسیله جوانه زنی کلاترال
  • 5. نقش JAK-STAT در پاسخ نورون محلی
  • 5.1. نقش JAK-STAT در بقای نورون
  • 5.2. تعدیل JAK-STAT محافظت نورونی در SCI
  • 6. نقش مسیر JAK-STAT در پاسخ گلیال
  • 6.1. سیتوکین ها پاسخ گلیال را در SCI تعدیل می کنند
  • 6.2. تعدیل STAT آستروسیت های واکنشی
  • 6.3. تعدیل JAK-STAT سلول های پیش ساز بنیادی عصبی
  • 7. نقش JAK-STAT در پاسخ التهابی
  • 7.1. سیتوکین های ضدالتهابی
  • 7.2. سیتوکین های پیش التهابی
  • 8. نتیجه گیری و پیامدهای بالینی

Abstract

JAK-STAT signalling is a main transduction pathway of cytokines and growth factors, which is involved in several biological processes including cell proliferation, cell differentiation, axon regeneration, apoptosis and inflammation. After spinal cord injury several cytokines activate the JAK-STAT pathway, thereby modulating several cell responses. In this chapter we discuss how regulation of this signalling pathway could improve motor recovery after injury by modulation of axon regeneration, neuroprotection, glial scar formation, demyelination and inflammatory response. Studies with gene over-expression, gene deletion and in vitro approaches will be discussed for understanding the cell-specific response to JAK-STAT signalling, with a focus on preclinical treatment with IL6-family cytokines, hematopoietic cytokines and IL10.

Keywords: - - - - -

8. Conclusion and clinical implications

Cytokine upregulation and JAK-STAT signalling activation are endogenous mechanism that are activated in response to SCI and can be used to improve motor recovery. Cell type specific and in vitro studies have identified the role of STATs modulation in spinal cord cells. STAT3 has been the most extensively studied STAT transcription factor in SCI, but promising results have been found in other STATs and further studies should continue to determine the roles of STAT1 and STAT5 in SCI. Moreover, further studies with transgenic models should focus in other specific cell responses not studied up to now, like motoneuron and NSPC responses.

Several preclinical studies have shown positive outcomes for motor recovery and tissue sparing in JAK-STAT cytokine treatments (Table 2). Thus, modulation of the JAK-STAT signalling presents an opportunity to modulate neuron and glial response after an SCI in clinical settings. The hematopoietic cytokines have been already used in clinical studies for several pathologies, therefore are advanced in comparison with other JAK-STAT cytokines. Discussion of G-CSF and EPO treatments for SCI can be found in previous chapters [45, 86], while for GM-CSF there is one SCI clinical study finished which consisted in cytokine administration with transplant of bone marrow cells [87]. Although clinical studies have not been assessed for other cytokines in CNS trauma, there are clinical studies involving other pathologies that could be translated to SCI. The anti-inflammatory and neuroprotective mechanism of IL10 could also be assessed with a recombinant human IL10 that has been used for HIV infection and other several pathologies [46]. Emfilermin is a recombinant human LIF that has been tested, although with a lack of effectiveness, in clinical trials for embryo implantation and peripheral neuropathy [88, 89] that could also be used in SCI or other CNS diseases. Finally, tocilizumab, an anti-human IL6R, has shown positive outcomes in clinical studies for rheumatoid arthritis [90] and could be used for anti-inflammatory treatment in the spinal cord acute response.

دانلود ترجمه تخصصی این مقاله دانلود رایگان فایل pdf انگلیسی