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Neuregulins: Versatile growth and differentiation factors in nervous system deve

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Brain Res Brain Res Rev. 2006 Jan 10

Neuregulins: Versatile growth and differentiation factors in nervous

system development and human disease.

Esper RM, Pankonin MS, Loeb JA.

Department of Neurology, Wayne State University, Detroit, MI, USA;

Center for Molecular Medicine and Genetics, Wayne State University,

Detroit, MI, USA.

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.

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