Regulation of neuronal cell death and differentiation by NGF and IAP family members.
Nerve growth factor (NGF) and other neurotrophins were identified because of their trophic role for distinct populations of neurons in the peripheral nervous system. We know that neuronal cell death is regulated by a genetically encoded programme, called apoptosis, that is conserved from worms to humans. Dysregulation of this programme is thought to contribute to neurodegenerative diseases which are characterized by the loss of neurons. This article will review recent findings about the motoneuron disease spinal muscular atrophy (SMA). Two closely linked candidate genes for SMA, the SMN (survival motor neuron) gene and the NAIP (neuronal apoptosis inhibitory protein) gene have been reported. The SMN protein forms a complex with several other proteins and this complex containing SMN plays a critical role in the assembly of spliceosomes and in pre-mRNA splicing. NAIP, c-IAP1 (inhibitor of apoptosis-1), c-IAP2, X-IAP and survivin comprise the mammalian inhibitor of apoptosis family. Its members can protect mammalian cells from apoptosis induced by a variety of stimuli. Some of the IAP molecules have been shown to interact both with cell signalling molecules and with specific caspases but details concerning their cellular role are only incompletely characterized.
Götz
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Klinische Forschergruppe Neuroregeneration, Department of Neurology, University of Würzburg, Federal Republic of Germany. goetz@mail.uni-wuerzburg.de
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D017362:Cyclic AMP Response Element-Binding Protein; D006801:Humans; D051379:Mice; D009410:Nerve Degeneration / Q000235:genetics*; D020932:Nerve Growth Factor / Q000235:genetics* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D051616:Neuronal Apoptosis-Inhibitory Protein; D016716:PC12 Cells / Q000378:metabolism; D016601:RNA-Binding Proteins; D051381:Rats; D055532:SMN Complex Proteins; D012689:Sequence Homology, Nucleic Acid; D014897:Spinal Muscular Atrophies of Childhood / Q000235:genetics*; D055533:Survival of Motor Neuron 1 Protein
D017362:Cyclic AMP Response Element-Binding Protein; C496800:NAIP protein, human; C496801:Naip1 protein, mouse; C496803:Naip6 protein, rat; D009419:Nerve Tissue Proteins; D051616:Neuronal Apoptosis-Inhibitory Protein; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526473:Smn1 protein, rat; D055533:Survival of Motor Neuron 1 Protein; D020932:Nerve Growth Factor