MAPKs: new targets for neurodegeneration

Expert Opin Ther Targets. 2003 Apr;7(2):187-200. doi: 10.1517/14728222.7.2.187.

Abstract

Neurodegenerative diseases remain a huge unmet pharmaceutical need. For some diseases such as Parkinson's disease, there are currently only palliative therapies, and for others such as Alzheimer's disease there are no proven therapies on the market that have any significant impact on disease progression. Recent work has suggested that cell death may play a key role in a number of neurodegenerative diseases, and halting this aberrant cell death may halt disease progression. Kinases identified in cell death pathways may be attractive targets for neurodegenerative diseases. In this review, the authors will focus on three families of related mitogen-activated protein kinases (MAPKs), namely, the extracellular signal-regulated protein kinases (ERKs), the c-Jun N-terminal kinases (JNKs) and the p38 MAPKs. The evidence for activation of each of these pathways in disease states and in models of neurodegenerative disorders will be examined. Effects of inhibitors, where available, will be discussed, and potential problems and side effects of kinase inhibitors as therapeutics will be addressed.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / enzymology
  • Apoptosis / drug effects
  • Brain Ischemia / drug therapy
  • Brain Ischemia / enzymology
  • Central Nervous System Agents / pharmacology*
  • Central Nervous System Agents / therapeutic use
  • Drug Design*
  • Humans
  • Huntington Disease / drug therapy
  • Huntington Disease / enzymology
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • JNK Mitogen-Activated Protein Kinases / physiology
  • MAP Kinase Signaling System / drug effects*
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinases / classification
  • Mitogen-Activated Protein Kinases / physiology
  • Models, Biological
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / enzymology
  • Nerve Degeneration / drug therapy*
  • Nerve Degeneration / enzymology
  • Nerve Tissue Proteins / antagonists & inhibitors*
  • Nerve Tissue Proteins / classification
  • Nerve Tissue Proteins / physiology
  • Parkinson Disease / drug therapy
  • Parkinson Disease / enzymology
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinase Inhibitors / therapeutic use

Substances

  • Central Nervous System Agents
  • Nerve Tissue Proteins
  • Protein Kinase Inhibitors
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases