Mixed-lineage kinases: a target for the prevention of neurodegeneration.
The activation of the c-Jun N-terminal kinase (JNK) pathway is critical for naturally occurring neuronal cell death during development and may be important for the pathological neuronal cell death of neurodegenerative diseases. The small molecule inhibitor of the mixed-lineage kinase (MLK) family of kinases, CEP-1347, inhibits the activation of the JNK pathway and, consequently, the cell death in many cell culture and animal models of neuronal death. CEP-1347 has the ability not only to inhibit cell death but also to maintain the trophic status of neurons in culture. The possible importance of the JNK pathway in neurodegenerative diseases such as Alzheimer's and Parkinson's diseases provides a rationale for the use of CEP-1347 for the treatment of these diseases. CEP-1347 has the potential of not only retarding disease progression but also reversing the severity of symptoms by improving the function of surviving neurons.
Wang
Leo H
LH
Departments of Neurology and Molecular Biology & Pharmacology, Washington University School of Medicine, Saint Louis, Missouri 63110-1031, USA.
Besirli
Cagri G
CG
Johnson
Eugene M
EM
D000544:Alzheimer Disease / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D034381:Hearing Loss / Q000503:physiopathology; D006801:Humans; D026121:Indole Alkaloids; D007211:Indoles / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000201:enzymology* / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010300:Parkinson Disease / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control
D002227:Carbazoles; D026121:Indole Alkaloids; D007211:Indoles; D018696:Neuroprotective Agents; C106592:3,9-bis((ethylthio)methyl)-K-252a; C049985:staurosporine aglycone; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases