JNK and p38 stresskinases - degenerative effectors of signal-transduction-cascades in the nervous system

The c-Jun N-terminal kinases (JNKs, also called stress activated protein ki nases, sAPKs) and p38 kinases constitute together with extracellular signal -regulated kinases (ERKs) the family of MAP kinases. Whereas the functions of JNKs under physiological conditions are largely unknown, there is raisin g evidence that JNKs are potent effecters of apoptosis or degeneration of n eurons in vitro and in the brain. The activation of the inducible transcrip tion factor c-Jun by N-terminal phosphorylation is a central event in JNK-m ediated degenerative processes that depend on de novo protein synthesis. At the post-translational level, cytoplasmic degenerative actions of JNKs mig ht comprise inhibition of Bcl-2 and steroid hormone-receptor signaling or h yperphosphorylation of tan, and at transcriptional level, JNKs might trigge r the induction of the apoptotic effectors p53 and Fas-Ligand by phosphoryl ation of c-Jun. The role of p38 is the nervous system is poorly understood, but its activation is also considered as part of the neuronal stress respo nse. This review informs about the genetic processing, the regulation of activit y and the biochemical actions of JNK and p38 isoforms in general. In the se cond part, we summarize the findings on expression and activation of JNKs a nd p38 under neurodegenerative condition. A particular focus is also put on the putative function of JNK under physiological conditions and for neurop rotection. (C) 2000 Elsevier Science Ltd. All rights reserved.