Akt/Protein Kinase B Prevents Injury-Induced Motoneuron Death and Accelerates Axonal Regeneration

摘要: Motoneurons require neurotrophic factors for their survival and axonal projection during development, as well nerve regeneration. By using the axotomy-induced neuronal death paradigm adenovirus-mediated gene transfer, we attempted to gain insight into functional significances of major growth factor receptor downstream cascades, Ras–extracellular signal-regulated kinase (Ras-ERK) pathway phosphatidylinositol-3 kinase–Akt (PI3K-Akt) pathway. After neonatal hypoglossal transection, constitutively active Akt-overexpressing neurons could survive those overexpressing Bcl-2, whereas ERK (MEK)-overexpressing ones failed survive. A dominant negative Akt experiment demonstrated that inhibition hastened in neonate. In addition, adult showed accelerated regeneration after axotomy. These results suggest plays dual roles motoneuronal vivo PI3K-Akt is probably more vital injury than Ras-ERK