Abstract
The loss of neurons is a hallmark of neurodegenerative disorders and evidence suggests that this occurs through an apoptotic mechanism. Following an insult, neuronal cells activate signal transduction pathways that lead to cell death and the establishment of the pathological state. The mechanisms underlying the cell-death response involve protein kinases, which phosphorylate many substrates and culminate in changes in gene expression. Traditionally, attempts at blocking such signaling targeted the phosphorylation of the substrates. However, preventing the interaction between two proteins using specific peptides might block the function of key mediators in signaling cascades. A cell-permeable peptide designed specifically to inhibit c-Jun N-terminal kinase action proved successful in in vivo models of neuronal degeneration following ischemia. Here, the recent findings that highlight the potential of this approach for therapeutic application are reviewed.
Publication types
-
Research Support, Non-U.S. Gov't
-
Review
MeSH terms
-
Animals
-
Apoptosis / drug effects
-
Cell Membrane Permeability
-
Humans
-
JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
-
JNK Mitogen-Activated Protein Kinases / metabolism
-
MAP Kinase Signaling System / drug effects
-
Nerve Degeneration / drug therapy*
-
Nerve Degeneration / metabolism
-
Nerve Degeneration / pathology
-
Neurons / drug effects*
-
Neurons / metabolism
-
Neurons / pathology
-
Neuroprotective Agents / metabolism
-
Neuroprotective Agents / pharmacology*
-
Neuroprotective Agents / therapeutic use
-
Peptides / metabolism
-
Peptides / pharmacology*
-
Peptides / therapeutic use
-
Phosphorylation
-
Protein Kinase Inhibitors / metabolism
-
Protein Kinase Inhibitors / pharmacology*
-
Protein Kinase Inhibitors / therapeutic use
-
Proto-Oncogene Proteins c-jun / metabolism
-
Signal Transduction / drug effects
Substances
-
Neuroprotective Agents
-
Peptides
-
Protein Kinase Inhibitors
-
Proto-Oncogene Proteins c-jun
-
JNK Mitogen-Activated Protein Kinases