JNK Signaling Pathway Involvement in Spinal Cord Neuron Development and Death

The c-Jun NH2-terminal protein kinase (JNK) is a Janus-faced kinase, which, in the nervous system, plays important roles in a broad range of physiological and pathological processes. Three genes, encoding for 10 JNK isoforms, have been identified: jnk1, jnk2, and jnk3. In the developing spinal cord, JNK proteins control neuronal polarity, axon growth/pathfinding, and programmed cell death; in adulthood they can drive degeneration and regeneration, after pathological insults. Indeed, recent studies have highlighted a role for JNK in motor neuron (MN) diseases, such as amyotrophic lateral sclerosis and spinal muscular atrophy. In this review we discuss how JNK-dependent signaling regulates apparently contradictory functions in the spinal cord, in both the developmental and adult stages. In addition, we examine the evidence that the specific targeting of JNK signaling pathway may represent a promising therapeutic strategy for the treatment of MN diseases.