Stem cell-derived neurotrophic support for the neuromuscular junction in spinal muscular atrophy.
BACKGROUND
Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by specific degeneration of α-motor neurons in the spinal cord. The use of cell transplantation to restore lost function through cell replacement or prevent further degeneration of motor neurons and synapses through neurotrophic support heralds tremendous hope in the SMA field.


METHODS
Much research has been carried out in the last decade on the use of embryonic stem cells in cell replacement strategies for various neurodegenerative diseases. Cell replacement is contingent on the ability of transplanted cells to integrate and form new functional connections with host cells. In the case of SMA, cell replacement is a tall order in that axons of transplanted cells would be required to grow over long distances from the spinal cord through growth-averse terrain to synapse with muscles in the periphery. The efficacy of neurotrophic support is contingent on the ability of transplanted cells to secrete neurotrophins appropriate for degenerating motor neurons in the spinal cord or development/stability of the neuromuscular junction (NMJ) in the periphery.


RESULTS
The reader will gain an understanding of the potential of neurotrophins to promote development of the NMJ in a diseased or injured environment.


CONCLUSIONS
Neurotrophins play a major role in NMJ development and thus may be a key factor in the pathogenesis of NMJs in SMA. Further research into the signaling mechanisms involved in NMJ maturation may identify additional mechanisms by which transplanted cells may be of therapeutic benefit.
Department of Anatomy and Neurobiology, University of California at Irvine, College of Medicine, Reeve-Irvine Research Center, Sue and Bill Gross Stem Cell Research Center, 2111 Gillespie Neuroscience Research Facility, Irvine, CA 92697-4292, USA.
Tanya J
TJ
Wyatt
Hans S
HS
Keirstead
D000818:Animals; D002454:Cell Differentiation; D000242:Cyclic AMP / Q000502:physiology; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000637:transplantation*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000473:pathology; D009410:Nerve Degeneration; D009414:Nerve Growth Factors / Q000502:physiology* / Q000627:therapeutic use; D055495:Neurogenesis; D009469:Neuromuscular Junction / Q000473:pathology*; D039904:Pluripotent Stem Cells / Q000637:transplantation; D021122:Protein Subunits; D011978:Receptors, Nicotinic / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D015290:Second Messenger Systems / Q000502:physiology; D014897:Spinal Muscular Atrophies of Childhood / Q000235:genetics / Q000473:pathology / Q000601:surgery*; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics; D013569:Synapses / Q000648:ultrastructure
D009414:Nerve Growth Factors; D021122:Protein Subunits; D011978:Receptors, Nicotinic; C526471:SMN1 protein, human; D055533:Survival of Motor Neuron 1 Protein; D000242:Cyclic AMP