Chemokines in the CNS: plurifunctional mediators in diverse states

The past decade has witnessed the remarkable ascendance of chemokines as pi votal regulatory molecules in cellular communication and trafficking. Evide nce increasingly implicates chemokines and chemokine receptors as plurifunc tional molecules that have a significant impact on the CNS. initially these molecules were bound 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 realizati on that, in addition to their role in pathological states, chemokines and t heir receptors have an important role in cellular communication in the deve loping and the normal adult CNS. For example, stromal-cell-derived factor I ,which is synthesized constitutively in the developing brain, has an obliga te role in neurone migration during the formation of the granule-cell layer of the cerebellum. Many chemokines are capable of directly regulating sign al-transduction pathways that ave involved in a variety of cellular functio ns, which range from synaptic transmission to growth. Clearly, the potentia l use of chemokines and their receptors as targets for therapeutic interven tion in CNS disease might now have to be considered in the context of the b roader physiological functions of these molecules.