The TAT protein transduction domain enhances the neuroprotective effect of glial-cell-line-derived neurotrophic factor after optic nerve transection.
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.
Kilic
Ulkan
U
Department of Neurology, Georg August University Göttingen, Göttingen, Germany.
Kilic
Ertugrul
E
Dietz
Gunnar P H
GP
Bähr
Mathias
M
D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D015696:Gene Products, tat / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000008:administration & dosage* / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D020221:Optic Nerve Injuries / Q000628:therapy*; D016133:Polymerase Chain Reaction; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000235:genetics; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology*; D014018:Tissue Distribution
D015696:Gene Products, tat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D011993:Recombinant Fusion Proteins; C505409:Casp3 protein, mouse; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases