Inhibition of calpains, by treatment with leupeptin, improves motoneuron survival and muscle function in models of motoneuron degeneration
Section snippets
Experimental procedures
All animals used in this study were bred and housed either in the Biological Services Unit at University College London or the Denny Brown Laboratories at the Institute of Neurology. Throughout this study all efforts were made to minimise the number of animals used and their suffering. All experiments described in this study were carried out under licence from the U.K. Home Office (Animals (Scientific Procedures) Act 1986) and following approval by the Ethical Review Panel of the Institute of
Results
The effect of leupeptin, a calpain inhibitor, on motoneuron survival was examined in vitro in an excitotoxic model of motoneuron degeneration, and also in vivo in a model of injury-induced motoneuron death.
Discussion
The results of this study show that treatment with leupeptin, an inhibitor of calpain proteases, rescues motoneurons in vitro following exposure to glutamate agonists and improves long-term motoneuron survival and muscle function in an in vivo model of injury-induced motoneuron degeneration.
Calpains have been described as cellular mediators of both necrotic (Wang, 2000) and apoptotic (Nath et al., 1996a,b) cell death. Early studies looking at the role of calpains in apoptosis showed that they
Acknowledgements
L.G. is the Graham Watts Senior Research Fellow. We are grateful to the Brain Research Trust for their support, D.K. is a BRT prize student. We would also like to thank Mr. James Dick, Dr. Jo Dekkers and Dr. Bernadett Kalmar for their assistance and expert advice.
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