The TAT Protein Transduction Domain Enhances the Neuroprotective Effect of Glial-Cell-Line-Derived Neurotrophic Factor after Optic Nerve Transection

被引:32
作者
Kilic, Uelkan [1 ]
Kilic, Ertugrul [1 ]
Dietz, Gunnar P. H. [1 ]
Baehr, Mathias [1 ]
机构
[1] Univ Gottingen, Univ Klinikum, Zentrum Neurol Med, Dept Neurol, DE-37075 Gottingen, Germany
关键词
Apoptosis; Glial-cell-line-derived neurotrophic factor; Neurodegeneration; Neurotrophin; Optic nerve axotomy; Protein transduction domain; Retinal ganglion cells; TAT fusion protein; Trojan horse peptide;
D O I
10.1159/000076669
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Glial-cell-line-derived neurotrophic factor (GDNF) acts as a potent survival factor for many neuronal populations, including retinal ganglion cells (RGC), indicating a potential therapeutic role of GDNF for neurological disorders. To enhance the tissue distribution and applicability of the neurotrophin, we linked it to a protein transduction domain derived from the HIV TAT protein and tested it in a well-established model for traumatic injury in the CNS: After optic nerve axotomy, the number of surviving RGCs was significantly increased in mice injected with TAT-GDNF on days 0, 3, 7, and 10 after surgery compared with GDNF- or PBS-injected animals. Moreover, TAT-GDNF reduced the number of activated caspase-3-positive cells. These results show that the neuroprotective effect of substances like neurotrophins may be enhanced by linking them to a domain that has been shown to mediate efficient transduction across biological membranes. Copyright (C) 2004 S. Karger AG, Basel
引用
收藏
页码:44 / 49
页数:6
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