Premium
Dual roles of the MAPK/ERK1/2 cell signaling pathway after stroke
Author(s) -
Sawe Nik,
Steinberg Gary,
Zhao Heng
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21604
Subject(s) - dual (grammatical number) , mapk/erk pathway , microbiology and biotechnology , signal transduction , neuroscience , biology , art , literature
Extracellular signal–regulated kinase 1/2 (ERK1/2), one of the best‐characterized members of the mitogen‐activated protein kinase (MAPK) family, mediates a range of activity from metabolism, motility, and inflammation to cell death and survival. It is phosphorylated and activated through a three‐tiered MEK mode via cell surface receptors stimulated by growth factors or cytokines. The phosphorylated ERK1/2 level is usually increased after cerebral ischemia/reperfusion, but whether an increase in ERK1/2 phosphorylation is protective or detrimental is highly debatable. Much of the support for ERK1/2's role as a neuroprotectant against stroke stems from its apparent involvement in the beneficial effects of growth factors, estrogen, preconditioning, and hypothermia on the ischemic brain. Conversely, evidence supporting the detrimental effects of ERK1/2 activity is derived from its activation promoting inflammation and oxidative stress and its inhibition reducing ischemic damage. The dual potential of ERK1/2 actions in the ischemic brain is likely related to its responses to a diverse array of agonists and cell surface receptors. Plausibly, the ERK1/2 activity generated by cytokines and free radicals or other inflammatory factors after stroke may worsen ischemic damage, whereas the ERK1/2 activity produced by exogenous growth factors, estrogen, and preconditioning favors neuroprotection. Future experiments should be conducted to optimize the protective effect of ERK1/2 while blocking its detrimental actions. © 2008 Wiley‐Liss, Inc.