Neurotrophins and ciliary neurotrophic factor: their biology and pathology

Neurotrophins (NTFs) and ciliary neurotrophic factor (CNTF) induce the differentiation of neuronal cells, rescue them from naturally occurring death, and trigger neuronal regeneration. The NTFs bind to two classes of cell surface receptors, whereas CNTF receptor is composed of three subunits. The functions of these polypeptide survival factors with trophic action on nerve cells have recently been approached by the targeted disruption of the CNTF, NTF and their receptor genes by the homologous recombination technique. The embryonic growth and morphogenesis of these gene 'knock-out' mice is normal, but they develop with defects in various subsets of the peripheral nervous system, and the homozygous mutant mice often die during the early postnatal period. Disturbances in the biology of NTFs and CNTF have recently been implicated in the pathogenesis of certain common neurodegenerative disorders, such as Parkinson's disease, motor neurone diseases, and Alzheimer's disease. Intensive research on their pharmaceutical perspective has, therefore, been provoked. All neurotrophins and CNTF can now be synthesized on a large scale as biologically active recombinant proteins, and several alternatives for their local applications to the target tissue have been presented. Their therapeutic potential is discussed.