کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8721426 1589404 2018 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The sneaking ligand approach for cell type-specific modulation of intracellular signalling pathways
ترجمه فارسی عنوان
رویکرد لیگاند دزدی برای مدولاسیون خاص سلول مسیرهای سیگنالینگ داخل سلولی
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
چکیده انگلیسی
Small molecules interfering with intracellular signalling pathways are used in the treatment of multiple diseases including RA. However, small molecules usually affect signalling in most cell types, not only in those which need to be targeted. This general inhibition of signalling pathways causes often adverse effects, which could be avoided by cell type-specific inhibitors. For cell-type specific modulation of signal transduction, we developed the sneaking ligand fusion proteins (SLFPs). SLFPs contain three domains: (1) the binding domain mediating cell type-specific targeting and endocytosis; (2) the endosomal release sequence releasing the effector domain into the cytoplasm; (3) the effector domain modulating signalling. Using our SLFP NF-kappaB inhibitor termed SLC1 we demonstrated that cell-type-specific modulation of intracellular signalling pathways is feasible, that endothelial NF-kappaB activation is critical for arthritis and peritonitis and that SLFPs help to identify disease-relevant pathways in defined cell types. Hence, SLFPs may improve risk-benefit ratios of therapeutic interventions.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Clinical Immunology - Volume 186, January 2018, Pages 14-20
نویسندگان
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