Brief Communication abstract
Nature Cell Biology 4, 175 - 179 (2002)
Published online: 28 January 2002 | doi:10.1038/ncb751
IAPs are essential for GDNF-mediated neuroprotective effects in injured motor neurons in vivo
D. Perrelet1, A. Ferri1, P. Liston3, P. Muzzin2, R.G. Korneluk3 & A.C. Kato1
During embryonic development, and in certain neurodegenerative diseases, neurons die by apoptosis1. A new family of anti-apoptotic proteins, termed inhibitors of apoptosis (IAP), suppresses apoptosis through the direct inhibition of caspases2, 3, 4, 5. The anti-apoptotic activity of IAPs is inhibited by second mitochondria-derived activator of caspase (Smac)/DIABLO6, 7 and XAF1 (ref. 8). IAPs, as well as neurotrophic factors, can protect degenerating neurons both in vivo and in vitro9, 10, 11, 12. However, the downstream targets of neurotrophic factors have not yet been identified. Here, we demonstrate that XIAP and NAIP, but not HIAP2, are directly involved in the intracellular response to glial cell-derived neurotrophic factor (GDNF). In newborn rats, GDNF regulates endogenous levels of XIAP and NAIP in motor neurons after sciatic nerve axotomy. The inhibition of XIAP or NAIP activity prevents GDNF-mediated neuroprotective effects. These results suggest that XIAP and NAIP are essential for intracellular signalling of GDNF in motor neuron survival.
- Division Clinical Neuromuscular Research & Dept. APSIC, Faculty of Medicine, 1 rue Michel Servet, 1211 Geneva 4, Switzerland
- Dept. Medical Biochemistry, Faculty of Medicine, 1 rue Michel Servet, 1211 Geneva 4, Switzerland
- Molecular Genetics Research Laboratory, Children's Hospital of Eastern Ontario and AEgera Therapeutics Inc., 401 Smith Road, Ottowa K1H8L1, Canada
Correspondence to: A.C. Kato1 e-mail: Ann.Kato@medecine.unige.ch
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