Neuronal p38 MAPK signalling: an emerging regulator of cell fate and function in the nervous system

p38 mitogen-activated protein kinases (MAPKs), together with extracellular signal-regulated kinases (ERKs) and c-Jun N-terminal kinases (JNKs), constitute the MAPK family. Multiple intracellular signalling pathways that converge on MAPKs exist in all eukaryotic cells and play pivotal roles in a wide variety of cellular functions. p38 MAPKs and JNKs, also termed stress-activated protein kinases (SAPKs), are preferentially activated by various cytotoxic stresses and cytokines and appear to be potent regulators of stress-induced apoptosis. Whereas JNKs have been shown to play pivotal roles in the regulation of neuronal apoptosis, the role of p38 MAPKs in the nervous system is poorly understood. However, accumulating evidence from mammalian cell culture systems and the strong genetic tool C. elegans suggests that neuronal p38 signalling has diverse functions beyond the control of cell death and survival. This review focuses on possible roles for the p38 pathway in the nervous system, with principal emphasis placed on the roles in neuronal cell fate decision and function.