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 injuri es 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 proper ties of the X-linked inhibitor of apoptosis protein (XIAP) to inhibit secon dary cell death after axonal lesions. We used adenoviral vectors to transdu ce retinal ganglion cells after axotomy of the optic nerve of adult rats. V ector application was performed at the optic nerve stump so that only the l esioned retinal neurons could be transduced. We found XIAP to be as effecti ve as the viral broad spectrum caspase inhibitor protein p35, These finding s suggest that axotomized RGCs degenerate through class II caspase activity and furthermore offer the possibility of using mammalian XIAP protein to i nhibit neuronal apoptosis as a basis for a regenerative therapy in the CNS.