Targeting JNK3 for the treatment of neurodegenerative disorders.
c-Jun N-terminal kinases (JNKs) have been recognized as important enzymes in cellular function. JNK3, which is predominantly found in CNS neurons, has been implicated in several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and stroke. In particular, JNK3 has been found to have an upstream role in neuronal ischemic apoptosis. JNK3 is highly expressed and activated in postmortem brains of individuals that suffered from Alzheimer's disease. Furthermore, mice that are deficient in JNK3 are more resistant to 1-methyl-4-phenyl-1,2,4,6-tetrahydropyridine (a neurotoxin that mimics the neuropathological characteristics of Parkinson's disease) than their wild-type littermates. Because of the involvement of JNK3 in neuronal diseases, the inhibition of this enzyme is an attractive therapeutic target.
Resnick
Lynn
L
Wyeth Research, CN 8000, Princeton, NJ 08543-8000, USA. resnick@wyeth.com
Fennell
Myles
M
D016503:Drug Delivery Systems / Q000379:methods*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D048057:Mitogen-Activated Protein Kinase 10 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000201:enzymology*
D004791:Enzyme Inhibitors; D048057:Mitogen-Activated Protein Kinase 10