Neurodegenerative and physiological actions of c-Jun N-terminal kinases in the mammalian brain

The research in the field of AP-1 transcription factor expression, such as Jun or Fos proteins, in the brain was a milestone in neurosciences. The last years have provided growing insights into the upstream signal transduction which controls the expression and activation of these transcriptional regulators. In particular, the c-Jun N-terminal kinases (JNKs) were considered to confer degeneration by activation of c-Jun. Recent findings, however, demonstrate an essential physiological role of JNKs in the nervous system. Here we review the specific control and dual functions of JNK isoforms which are relevant for the development of the intact brain on the one hand, and which can confer dramatic neurodegenerative effects and microglial activation on the other hand. (C) 2004 Published by Elsevier Ireland Ltd.