کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10930068 | 1093377 | 2015 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Ciliary neurotrophic factor (CNTF): New facets of an old molecule for treating neurodegenerative and metabolic syndrome pathologies
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کلمات کلیدی
PI3KIFNγIL6gp130AMPKCNTFmTORBHKLIFRCNTFRAMP-activated protein kinase - AMP-پروتئین کیناز فعال شده استERK1/2 - ERK1 / 2MAPK - MAPKSTAT - آمارinterleukin-6 - اینترلوکین ۶ciliary neurotrophic factor - فاکتور نوروتروفیک ciliaryphosphoinositide 3-kinase - فسفینوزیتید 3-کینازLow-density lipoprotein - لیپوپروتئین کم چگالی یا الدیال LDL - لیپوپروتئین کم چگالی(کلسترول بد)signal transducers and activators of transcription - مبدل سیگنال و فعال کننده رونویسیmammalian target of rapamycin - هدف پستانداران رپامایسینJAK - چگونهJanus kinases - ژنوس کینازmitogen-activated protein kinases - کیناز پروتئین فعال Mitogenextracellular signal-regulated kinases 1 and 2 - کینازهای 1 و 2 تنظیم شده سیگنال خارج سلولیInterferon gamma - گاما اینترفرونCiliary neurotrophic factor receptor - گیرنده فاکتور فاکتور نورودرمانی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
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چکیده انگلیسی
Ciliary neurotrophic factor (CNTF) is the most extensively studied member of the cytokine family that signal through intracellular chains of the gp130/LIFRβ receptor. The severe phenotype in patients suffering from mutations inactivating LIFRβ indicates that members of this cytokine family play key, non-redundant roles during development. Accordingly, three decades of research has revealed potent and promising trophic and regulatory activities of CNTF in neurons, oligodendrocytes, muscle cells, bone cells, adipocytes and retinal cells. These findings led to clinical trials to test the therapeutic potential of CNTF and CNTF derivatives for treating neurodegenerative and metabolic diseases. Promising results have encouraged continuation of studies for treating retinal degenerative diseases. Results of some clinical trials showed that side-effects may limit the systemically administrated doses of CNTF. Therefore, therapies being currently tested rely on local delivery of CNTF using encapsulated cytokine-secreting implants. Since the side effects of CNTF might be linked to its ability to activate the alternative IL6Rα-LIFRβ-gp130 receptor, CNTFR-specific mutants of CNTF have been developed that bind to the CNTFRα-LIFRβ-gp130 receptor. These developments may prove to be a breakthrough for therapeutic applications of systemically administered CNTF in pathologies such as multiple sclerosis or Alzheimer's disease. The “designer cytokine approach” offers future opportunities to further enhance specificity by conjugating mutant CNTF with modified soluble CNTFRα to target therapeutically relevant cells that express gp130-LIFRβ and a specific cell surface marker.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cytokine & Growth Factor Reviews - Volume 26, Issue 5, October 2015, Pages 507-515
Journal: Cytokine & Growth Factor Reviews - Volume 26, Issue 5, October 2015, Pages 507-515
نویسندگان
Sarah Pasquin, Mukut Sharma, Jean-François Gauchat,