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Publication : Local axonal function of STAT3 rescues axon degeneration in the pmn model of motoneuron disease.

First Author  Selvaraj BT Year  2012
Journal  J Cell Biol Volume  199
Issue  3 Pages  437-51
PubMed ID  23109669 Mgi Jnum  J:195255
Mgi Id  MGI:5476913 Doi  10.1083/jcb.201203109
Citation  Selvaraj BT, et al. (2012) Local axonal function of STAT3 rescues axon degeneration in the pmn model of motoneuron disease. J Cell Biol 199(3):437-51
abstractText  Axonal maintenance, plasticity, and regeneration are influenced by signals from neighboring cells, in particular Schwann cells of the peripheral nervous system. Schwann cells produce neurotrophic factors, but the mechanisms by which ciliary neurotrophic factor (CNTF) and other neurotrophic molecules modify the axonal cytoskeleton are not well understood. In this paper, we show that activated signal transducer and activator of transcription-3 (STAT3), an intracellular mediator of the effects of CNTF and other neurotrophic cytokines, acts locally in axons of motoneurons to modify the tubulin cytoskeleton. Specifically, we show that activated STAT3 interacted with stathmin and inhibited its microtubule-destabilizing activity. Thus, ectopic CNTF-mediated activation of STAT3 restored axon elongation and maintenance in motoneurons from progressive motor neuronopathy mutant mice, a mouse model of motoneuron disease. This mechanism could also be relevant for other neurodegenerative diseases and provide a target for new therapies for axonal degeneration.
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