[Nerve growth factors: a hypothesis on their role in the pathogenesis of infantile spinal amyotrophies].
The spinal muscular atrophies (SMA) are inherited neurological disorders characterized by degeneration and atrophy of spinal motoneurons at infant and juvenile stages. The origin of these diseases, and the mechanism of their progression, are completely unknown. Nevertheless, the selective neuronal loss which characterizes them is reminiscent of a classical experimental observation: injection of antibodies to the Nerve Growth Factor (NGF) in neonatal rats results in the almost complete selective destruction of the sympathetic nervous system. NGF is one of a group of molecules, the neuronal growth factors, which most likely play a role in the regulation of neuron number and development in different parts of the nervous system. In particular, several in vivo and in vitro results suggest that muscle may at certain stages produce "motoneuron growth factors". Our hypothesis is that the motoneuron death observed in the spinal muscular atrophies may be accelerated (or perhaps brought about) by a malfunction in this trophic support system. We show how this model would explain the perinatal or infantile onset of the disease, the variability of the rate of evolution between the different SMA forms, and the fact that motoneuron loss is much more dramatic in SMA than in even advanced cases of myopathy. We raise the possibility that the genetic lesion that leads to the spinal muscular atrophies may directly involve the growth factor system. Preliminary results obtained in vitro using cultures of embryonic chick spinal neurons do indeed suggest that muscle of SMA patients contains substances that inhibit muscle-derived growth-promoting activities. However, such phenomena must be interpreted with caution until the neurons and molecules involved are better characterized.
Henderson
C E
CE
Neurobiologie Moléculaire, Institut Pasteur, Paris.
Fardeau
M
M
D006801:Humans; D008959:Models, Neurological; D009046:Motor Neurons / Q000502:physiology; D009134:Muscular Atrophy, Spinal / Q000209:etiology*; D009414:Nerve Growth Factors / Q000502:physiology*; D014897:Spinal Muscular Atrophies of Childhood / Q000209:etiology*
D009414:Nerve Growth Factors
Les facteurs de croissance nerveuse: une hypothèse sur leur rôle dans la pathogénie des amyotrophies spinales infantiles.