Mixed-Lineage Kinases: A Target for the Prevention of Neurodegeneration

Abstract

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.