Activation of MAPK ERK in peripheral nerve after injury

Phosphorylation of ERK in the sciatic nerve in several time-points after crush injury has been examined. Higher phosphorylation of ERK was observed in the proximal and distal nerve stumps compared to the contralateral intact nerve from one day to one month after crush. The activation of ERK was mainly localized in the axons of the proximal segments. In the distal segments, however, active ERK was predominantly found in Schwann cells forming Bungner's bands.The findings indicate that ERK is activated in both the proximal and distal nerve stumps following nerve injury. The role of activated ERK in Wallerian degeneration and subsequent regeneration in vivo remains to be elucidated.Peripheral axotomy can activate several signaling pathways in neurons and associated glial cells leading to two opposing consequences: cell death or adaptation to regenerate neurites. The principal signaling pathways that have been demonstrated to be involved in axonal regeneration are PI3K-Akt [1-3] and JAK/STAT [4,5].Accumulated evidence has shown the participation of mitogen-activated protein kinases (MAPKs) during axonal injuries. MAPKs are a family of serine/threonine specific kinases that transduce extracellular stimuli to altered gene expression and have been shown to play a role in diverse cellular events ranging from proliferation, differentiation to apoptosis. So far, three subfamilies of MAPKs have been identified, namely: extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK) and p38 kinase (p38). JNK along with its main transcription factor, c-Jun, are activated in the dorsal root ganglia (DRG) after sciatic nerve transection [6-8]. Similarly, it has been reported that p38 was activated in axotomized neurons and, in case of spinal root ligation, this activation has been linked to the development of mechanical allodynia [9-11]. Moreover, inhibition of p38 leads to enhanced axonal regeneration, suggesting that p38 is likely involved in this process [12].As for