These authors contributed equally to this study.
JNK2 and JNK3 combined are essential for apoptosis in dopamine neurons of the substantia nigra, but are not required for axon degeneration
Version of Record online: 3 OCT 2008
© 2008 The Authors. Journal Compilation © 2008 International Society for Neurochemistry
Journal of Neurochemistry
Volume 107, Issue 6, pages 1578–1588, December 2008
How to Cite
Ries, V., Silva, R. M., Oo, T. F., Cheng, H.-C., Rzhetskaya, M., Kholodilov, N., Flavell, R. A., Kuan, C.-Y., Rakic, P. and Burke, R. E. (2008), JNK2 and JNK3 combined are essential for apoptosis in dopamine neurons of the substantia nigra, but are not required for axon degeneration. Journal of Neurochemistry, 107: 1578–1588. doi: 10.1111/j.1471-4159.2008.05713.x
- Issue online: 24 NOV 2008
- Version of Record online: 3 OCT 2008
- Received August 4, 2008; revised manuscript received September 10, 2008; accepted September 18, 2008.
- mitogen-activated protein kinase;
- Parkinson’s disease;
- programmed cell death
Activation of c-jun N-terminal kinase (JNK) by the mitogen-activated protein kinase cascade has been shown to play an important role in the death of dopamine neurons of the substantia nigra, one of the principal neuronal populations affected in Parkinson’s disease. However, it has remained unknown whether the JNK2 and JNK3 isoforms, either singly or in combination, are essential for apoptotic death, and, if so, the mechanisms involved. In addition, it has been unclear whether they play a role in axonal degeneration of these neurons in disease models. To address these issues we have examined the effect of single and double jnk2 and jnk3 null mutations on apoptosis in a highly destructive neurotoxin model, that induced by intrastriatal 6-hydroxydopamine. We find that homozygous jnk2/3 double null mutations result in a complete abrogation of apoptosis and a prolonged survival of the entire population of dopamine neurons. In spite of this complete protection at the cell soma level, there was no protection of axons. These studies provide a striking demonstration of the distinctiveness of the mechanisms that mediate cell soma and axon degeneration, and they illustrate the need to identify and target pathways of axon degeneration in the development of neuroprotective therapeutics.