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Agrin in the CNS: a protein in search of a function?

The extracellular matrix molecule agrin mediates the motor neuron induced accumulation of acetylcholine receptors (AChR) at the neuromuscular junction. Agrin is also present in the CNS. However, while its spatiotemporal pattern of expression is consistent with a function in neuron–neuron synapse formation, it also suggests a role for agrin in other aspects of neural tissue morphogenesis. Here we review the data supporting these synaptic and non-synaptic functions of agrin in the CNS. The results of studies aimed at identifying a neuronal receptor for agrin (NRA) and its associated signal transduction pathways are examined. Possible roles for agrin in the etiology of diseases affecting the brain are also discussed.