[Motoneuronal cell death and neurotrophic factors]

At early developmental stages, the survival of motoneurons is maintained by some as yet unidentified neurotrophic factors derived from their target muscles. As the animal matures, motoneuronal survival becomes less dependent on the innervated muscle. Yet, the dependence of motoneuronal survival on the target muscle does not abolish completely even in adults. In man, more than 50% of the lumbar motoneurons die several years after leg amputation. Thus, in principle, motoneuron disease can result from prolonged impairment of the neurotrophic supply from the target muscle. Several candidates have been proposed for the trophic factor of motoneurons; these include CNTF (ciliary neurotrophic factor), the FGF (fibroblast growth factor) family, the neurotrophin family and CADF (choline acetyltransferase development factor). CNTF is now considered to be a lesion factor rather than a neurotrophic factor. In the FGF family, FGF-5 remains as a possible neurotrophic factor for motoneurons. Three neurotrophins, BDNF (brain-derived neurotrophic factor), neurotrophin 3 (NT-3) and NT-5, may support the survival of both sensory neurons and motoneurons. CADF is a strong candidate, but its primary structure remains unknown.