Pigment epithelium-derived factor promotes the survival and differentiation of developing spinal motor neurons

Pigment epithelium-derived factor (PEDF) is a member of the serine protease inhibitor (serpin) superfamily that has been shown previously to promote t he survival and/or differentiation of rat cerebellar granule neurons and hu man retinoblastoma cells in vitro. However, in contrast to most serpins, PE DF has no inhibitory activity against any known proteases and its described biological activities do not appear to require the serpin-reactive loop lo cated toward the carboxy end of the polypeptide. Because another serpin, pr otease nexin-l, has been shown to promote the in vivo survival and growth o f motor neurons, the authors investigated the potential neurotrophic effect s of PEDF on spinal cord motor neurons in highly enriched cultures and in v ivo after injury. Here, it is shown that native bovine and recombinant huma n PEDF promoted the survival and differentiation (neurite outgrowth) of emb ryonic chick spinal cord motor neurons in vitro in a dose-dependent manner. A truncated form of PEDF that lacks approximate to 62% of the carboxy end of the polypeptide comprising the homologous serpin-reactive loop also exhi bited neurotrophic activities similar to those of the full-length protein. Furthermore, the data here showed that PEDF was transported retrogradely an d prevented the death and atrophy of spinal motor neurons in the developing neonatal mouse after axotomy. These results indicate that PEDF exerts trop hic effects on motor neurons, and, together with previous reports, these fi ndings suggest that this protein may be useful as a pharmacologic agent to promote the development and maintenance of motor neurons. Published 1999 Wi ley-Liss, Inc.dagger.