CILIARY NEUROTROPHIC FACTOR

Ciliary neurotrophic factor (CNTF) was first identified and partially purified from embryonic chick eye tissues. Subsequently, it was shown that CNTF is also present in large amounts in sciatic nerves of adult rats and rabbits, which led to its final purification and cloning. CNT F is not secreted by the classical secretory pathway involving the end oplasmatic reticulum and Golgi complex, but can be detected in high qu antities within the cytoplasm of myelinating Schwann cells and astrocy tes using immunohistochemistry. CNTF supports survival and/or differen tiation of a variety of neuronal cell types including sensory, sympath etic, and motoneurons. Also, nonneuronal cells, such as oligodendrocyt es, microglial cells, liver cells, and skeletal muscle cells, respond to exogenously administered CNTF, both in vitro and in vivo. During de velopment, expression of CNTF is very low, if indeed it is expressed a t all, and the phenotype of mice lacking endogenous CNTF after inactiv ation of the CNTF gene by homologous recombination suggests that CNTF does not play a crucial role for responsive cells during embryonic dev elopment. However, motoneurons are lost postnatally in mice lacking en dogenous CNTF, suggesting that CNTF acts physiologically on the mainte nance of these cells. The ability of exogenous CNTF to protect against motoneuron loss following lesion or in other animal models indicates that CNTF might be useful in the treatment of human motoneuron disorde rs, provided appropriate means of administration can be found. (C) 199 4 John Wiley & Sons, Inc.