Neuregulins: versatile growth and differentiation factors in nervous system development and human disease

The neuregulins are a family of growth and differentiation factors with a wide range of functions in the nervous system. The power and diversity of the neuregulin signaling system comes in part from a large number of alternatively-spliced forms of the NRG1 gene that can produce both soluble and membrane-bound forms. The soluble forms of neuregulin are unique from other factors in that they have a structurally distinct heparin-binding domain that targets and potentiates its actions. In addition, a finely tuned, bidirectional mechanism regulates when and where neuregulin is released from neurons in response to neurotrophic factors produced by both neuronal targets and supporting glial cells. Together, this produces a balanced intercellular signaling system that can be localized to distinct regions for both normal development and maintenance of the mature nervous system. Recent evidence suggests that neuregulin signaling plays important roles in many neurological disorders including multiple sclerosis, traumatic brain and spinal cord injury, peripheral neuropathy, and schizophrenia. Here, we review the basic biology of neuregulins and relate this to research suggesting their involvement with and potential therapeutic uses for neurological disorders.