The X-linked inhibitor of apoptosis (XIAP) prevents cell death in axotomized CNS neurons in vivo.
The inhibition of neuronal apoptosis in acute traumatic and ischemic injuries as well as in long term neurodegenerative disorders like spinal muscular atrophy and possibly Alzheimer's disease is a fundamental requirement for a therapeutic strategy. In this study we used an established in vivo model system of induction of neuronal apoptosis in the CNS to evaluate the properties of the X-linked inhibitor of apoptosis protein (XIAP) to inhibit secondary cell death after axonal lesions. We used adenoviral vectors to transduce retinal ganglion cells after axotomy of the optic nerve of adult rats. Vector application was performed at the optic nerve stump so that only the lesioned retinal neurons could be transduced. We found XIAP to be as effective as the viral broad spectrum caspase inhibitor protein p35. These findings suggest that axotomized RGCs degenerate through class II caspase activity and furthermore offer the possibility of using mammalian XIAP protein to inhibit neuronal apoptosis as a basis for a regenerative therapy in the CNS.
Kügler
S
S
Department of Neurology, University of Tuebingen, Medical School Verfuegungsgebaeude, Auf der Morgenstelle 15, 72076 Tuebingen, Germany. kuegler@uni.tuebingen.de
Straten
G
G
Kreppel
F
F
Isenmann
S
S
Liston
P
P
Bähr
M
M
D000818:Animals; D017209:Apoptosis; D019771:Axotomy; D002470:Cell Survival; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D009474:Neurons / Q000502:physiology*; D009900:Optic Nerve; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D051381:Rats; D012160:Retina / Q000033:anatomy & histology / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019076:Transgenes / Q000235:genetics; D051636:X-Linked Inhibitor of Apoptosis Protein
D011506:Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; D012313:RNA