Akt/protein kinase B prevents injury-induced motoneuron death and accelerates axonal regeneration.
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| Abstract |
Motoneurons require neurotrophic factors for their survival and axonal projection during development, as well as nerve regeneration. By using the axotomy-induced neuronal death paradigm and adenovirus-mediated gene transfer, we attempted to gain insight into the functional significances of major growth factor receptor downstream cascades, Ras-extracellular signal-regulated kinase (Ras-ERK) pathway and phosphatidylinositol-3 kinase-Akt (PI3K-Akt) pathway. After neonatal hypoglossal nerve transection, the constitutively active Akt-overexpressing neurons could survive as well as those overexpressing Bcl-2, whereas the constitutively active ERK kinase (MEK)-overexpressing ones failed to survive. A dominant negative Akt experiment demonstrated that inhibition of Akt pathway hastened axotomy-induced neuronal death in the neonate. In addition, the dominant active Akt-overexpressing adult hypoglossal neurons showed accelerated axonal regeneration after axotomy. These results suggest that Akt plays dual roles in motoneuronal survival and nerve regeneration in vivo and that PI3K-Akt pathway is probably more vital in neuronal survival after injury than Ras-ERK pathway.
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| Authors | K Namikawa, M Honma, K Abe, M Takeda, K Mansur, T Obata, A Miwa, H Okado, H Kiyama |
| Journal | The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 20 Issue 8 Pg. 2875-86 (Apr 15 2000) ISSN: 1529-2401 [Electronic] United States |
| PMID | 10751440 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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