Targeting the JNK pathway for therapeutic benefit in CNS disease.
The c-Jun N-terminal Kinase (JNK) pathway leading to c-Jun phosphorylation plays a causal role in apoptosis of isolated primary embryonic neurons and of multiple neuronal cell lines following a wide variety of stimuli. Activation of this pathway may also contribute to the neuronal atrophy and death that is associated with neurodegenerative pathological conditions including Alzheimer's, Parkinson's, Huntington's Diseases and stroke. Here, the data that providelinks between the activation of the JNK pathway and its potential to play an operative role in CNS disease are reviewed. Also included is the progress on development of inhibitors targeting the JNK pathway for therapeutic benefit.
Bozyczko-Coyne
Donna
D
Cephalon Inc, West Chester, PA 19380, USA. dbozyczk@cephalon.com
Saporito
Michael S
MS
Hudkins
Robert L
RL
D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000627:therapeutic use; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000201:enzymology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D004791:Enzyme Inhibitors; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases