IAP family proteins delay motoneuron cell death in vivo

Neuronal apoptosis inhibitory protein (NAIP), and human inhibitors of apopt osis 1 and 2 (HIAP1 and HIAP2) are three members of the mammalian family of antiapoptosis proteins called 'inhibitors of apoptosis' (IAP). These molec ules can prevent apoptosis in vitro and the over-expression of NAIP can dec rease ischemic damage in the hippocampus. The goal of our experiments was t o determine whether administration of NAIP, HIAP1 and HAIP2 could rescue mo toneurons following axotomy of a peripheral nerve. In young rats, an adenov iral gene transfer technique was used to deliver and express these proteins in motoneurons; a fluorescent tracer was simultaneously added as a means f or quantitatively assessing the rescue of fluorescently labelled motoneuron s in serial sections of the lumbar spinal cord. Control experiments using a denoviral vectors (adv) expressing the lacZ gene showed that 14% of the sci atic motoneuron pool could be transfected indicating the existence of a sub population of spinal motoneurons susceptible to this class of viral vectors . The administration of an adv-NAIP, adv-HIAP1 and adv-HIAP2 rescued 30-40% of motoneurons at one week after sciatic axotomy. The efficiency of these proteins was similar to that of two neurotrophic factors, ciliary neurotrop hic factor and brain-derived neurotrophic factor, administrated by the same viral technique. The effect of the IAP proteins on motoneuron survival dec reased with time but was still present after 4 weeks postaxotomy; the durat ion of the response was dependent upon the viral titre. These experiments d emonstrate that IAP family proteins can prevent motoneuron cell death in vi vo and may offer a new therapeutic approach for motoneuron diseases.