Mitogen-activated protein kinases and cerebral ischemia

Mol Neurobiol. 2001 Feb;23(1):1-19. doi: 10.1385/MN:23:1:01.

Abstract

Mitogen-activated protein kinases (MAPKs) have crucial roles in signal transduction from the cell surface to the nucleus and regulate cell death and survival. Recent papers support the hypothesis that neuronal apoptosis and cerebral ischemia induce the robust activation of MAPK cascades. Although extracellular signal-regulated kinases pathways promote cell survival and proliferation, and c-Jun N-terminal protein kinases/p38 pathways induce apoptosis in general, the roles of MAPK cascades in neuronal death and survival seem to be complicated and altered by the type of cells and the magnitude and timing of insults. Some specific inhibitors of MAPK cascades provide important information in clarifying the roles of each molecule in neuronal death and survival, but the results are still controversial. Further studies are necessary to elucidate the activated signal transduction upstream and downstream of the cascades in cerebral ischemia, and to define the crosstalk between the cascades and other signaling pathways, before MAPK cascades can be candidate molecules in the treatment of cerebral ischemia.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Brain Ischemia / drug therapy
  • Brain Ischemia / enzymology*
  • Brain Ischemia / pathology
  • Calcium Signaling
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Gene Expression Regulation
  • Growth Substances / physiology
  • Hippocampus / blood supply
  • Hippocampus / enzymology
  • Hippocampus / pathology
  • Humans
  • Ischemic Preconditioning
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Signaling System* / drug effects
  • Mitogen-Activated Protein Kinase 1 / physiology
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinases / physiology
  • Models, Biological
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / physiology
  • Neurons / drug effects
  • Neurons / enzymology
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • PC12 Cells / enzymology
  • PC12 Cells / metabolism
  • Phosphorylation / drug effects
  • Protein Processing, Post-Translational / drug effects
  • Rats
  • Receptors, Glutamate / physiology
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Enzyme Inhibitors
  • Growth Substances
  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • Receptors, Glutamate
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases