Many neurological disorders are characterised by structural changes in neuronal connections, ranging from presymptomatic synaptic changes to the loss or rewiring of entire axon bundles. The molecular mechanisms that underlie this perturbed connectivity are poorly understood, but recent studies suggest a role for axon guidance proteins. Axon guidance proteins guide growing axons during development and control structural plasticity of synaptic connections in adults. Changes in expression or function of these proteins might induce pathological changes in neural circuits that predispose to, or cause, neurological diseases. For some neurological disorders, such as midline crossing disorders, investigators have identified causative mutations in genes for axon guidance. However, for most other disorders, evidence is correlative and further studies are needed to confirm the pathological role of defects in proteins for axon guidance. Importantly, further insight into how dysregulation of axon guidance proteins causes disease will help the development of therapeutic strategies for neurological disorders.
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