Chemokines in the CNS: plurifunctional mediators in diverse states

The past decade has witnessed the remarkable ascendance of chemokines as pivotal regulatory molecules in cellular communication and trafficking. Evidence increasingly implicates chemokines and chemokine receptors as plurifunctional molecules that have a significant impact on the CNS. Initially, these molecules were found to be involved in the pathogenesis of many important neuroinflammatory diseases that range from multiple sclerosis and stroke to HIV encephalopathy. However, more-recent studies have fuelled the realization that, in addition to their role in pathological states, chemokines and their receptors have an important role in cellular communication in the developing and the normal adult CNS. For example, stromal-cell-derived factor 1, which is synthesized constitutively in the developing brain, has an obligate role in neurone migration during the formation of the granule-cell layer of the cerebellum. Many chemokines are capable of directly regulating signal-transduction pathways that are involved in a variety of cellular functions, which range from synaptic transmission to growth. Clearly, the potential use of chemokines and their receptors as targets for therapeutic intervention in CNS disease might now have to be considered in the context of the broader physiological functions of these molecules.