The JNK and p38 signal transduction following axotomy

Abstract

The transection of nerve fibers evokes a characteristic reaction in the injured neurons, the so-called cell body response (CBR), which com-prises aspects of developmental re-differentiation with parallel loss of the transmittory phenotype, efforts or achievement of axonal elongation and re-construction of effective synapses. Neither the signals underlying the onset of CBR nor the programs underlying regeneration are suffi-ciently elucidated. Here we review the putative role of two subfamilies of the MAP kinases, the JNKs (c-Jun N-terminal kinases) and the p38 kinases in the CBR. Following nerve injury with subsequent CBR, JNKs are rapidly activated and this activation persists for weeks until neu-ronal cell death or successful regeneration. The various functions render JNKs to perfect candidate molecules for the realization of the CBR including axonal transport, activation of c-Jun, modulation of cytoskeletal functions, detection of cytoskeletal alterations, or signal transduc-tion of adhesion molecules in the axon and growth cone. On the other hand, the rapid but transient activation of p38 might interfere with the mitotic arrest, a putative feature of the CBR.