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Pigment epithelium-derived factor promotes the survival and differentiation of developing spinal motor neurons
L J Houenou1, A P D'Costa, L Li
1Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. lhouenou@wfubmc.edu
Insights
Pigment epithelium-derived factor (PEDF) promotes motor neuron survival and differentiation. This neurotrophic factor, PEDF, shows promise for developing and maintaining motor neurons, even after injury.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Pigment epithelium-derived factor (PEDF) is a serpin superfamily member with known roles in neuronal survival.
- Unlike typical serpins, PEDF lacks protease inhibitory activity, suggesting unique functions.
- Previous studies showed protease nexin-1 promotes motor neuron survival in vivo.
Purpose of the Study:
- To investigate the neurotrophic effects of PEDF on spinal cord motor neurons.
- To determine if PEDF promotes survival and differentiation of motor neurons in vitro and in vivo.
Main Methods:
- Enriched cultures of embryonic chick spinal cord motor neurons were used.
- In vivo studies involved neonatal mouse spinal cord axotomy.
- Both native bovine and recombinant human PEDF were tested, including a truncated form.
Main Results:
- PEDF significantly promoted motor neuron survival and neurite outgrowth in vitro.
- A truncated PEDF lacking the serpin-reactive loop retained neurotrophic activity.
- In vivo, PEDF was retrogradely transported and prevented motor neuron death and atrophy post-axotomy.
Conclusions:
- PEDF exhibits significant trophic effects on motor neurons.
- These findings suggest PEDF's potential as a therapeutic agent for motor neuron development and maintenance.
- PEDF's neurotrophic activity may not depend on its serpin-reactive loop.
Abstract:
Pigment epithelium-derived factor (PEDF) is a member of the serine protease inhibitor (serpin) superfamily that has been shown previously to promote the survival and/or differentiation of rat cerebellar granule neurons and human retinoblastoma cells in vitro. However, in contrast to most serpins, PEDF has no inhibitory activity against any known proteases, and its described biological activities do not appear to require the serpin-reactive loop located toward the carboxy end of the polypeptide. Because another serpin, protease nexin-1, has been shown to promote the in vivo survival and growth of motor neurons, the authors investigated the potential neurotrophic effects of PEDF on spinal cord motor neurons in highly enriched cultures and in vivo after injury. Here, it is shown that native bovine and recombinant human PEDF promoted the survival and differentiation (neurite outgrowth) of embryonic chick spinal cord motor neurons in vitro in a dose-dependent manner. A truncated form of PEDF that lacks approximately 62% of the carboxy end of the polypeptide comprising the homologous serpin-reactive loop also exhibited neurotrophic activities similar to those of the full-length protein. Furthermore, the data here showed that PEDF was transported retrogradely and prevented the death and atrophy of spinal motor neurons in the developing neonatal mouse after axotomy. These results indicate that PEDF exerts trophic effects on motor neurons, and, together with previous reports, these findings suggest that this protein may be useful as a pharmacologic agent to promote the development and maintenance of motor neurons. J. Comp. Neurol. 412:506-514, 1999. Published 1999 Wiley-Liss, Inc.