Construction Of CT-1/TTC Fusion Protein And It's Effect On Spinal Cord Injury

Nowdays,spinal cord injury(SCI) has more important effect on our society,and make a great loss.however ,lack of effective therapeutic methods leading to deterioration.Cardiotrophin-1,a newly isolated member of the interleutin(IL)-6-related cytokine family,which includes IL-6 and leukemia inhibitory factor(LIF),is a potent inducer of cardiac myocyte hypertrophy and gene expression.CT-1,via coupling through the LIF receptor and gp130,has been shown to activate a number of signaling pathways in cardiac myocytes,including mitogen-activated protein kinases and the Janus kinase(JAK)/signal transducers and activators of translocate to nucleus,and activate expression of target genes.in addition,cardiotrophin-1 can delay motor defect of mice and exert protective effect against loss of proximal motor axons.Consequently,they share many biological activities on hematopoietic cells,embryonic stem cells,and hepatocytes. Thus,chronic administration of cytokines to animals induces pleiotropic effects including weight loss and synthesis of acute-phase proteins.These results suggested that neuro- protective effects of cytokines might be counter-balanced by their systemic toxicity.Tetanus toxin(TeNT),a potent neurotoxin produced by the anaerobic bacterium Clostridium tetani, causes spastic paralysis by blocking the neurotransmitter release from spinal cord interneurons. TeNT has a well-documented capacity for neuronal binding and internalization.When administered to animals,the toxin is taken up selectively by nerve endings at the neuromuscular junction and gains access to the CNS via retrograde axonal transport within motoneurons and trans-synaptic migration to interneurons.The 150-kDa TeNT protein is composed of a heavy chain which mediates binding and retrograde transport and light chain which is responsible for most of the toxicity.The TTC fragment,corresponding to the carboxy-terminal 451-amino-acid fragment of the heavy chain ,retains the neuronal binding and uptake properties of the holotoxin but is nontoxic, Thus it has been proposed that TTC could be used to target and deliver proteins to...