, Volume 226, Issue 2, pp 201–215 | Cite as

Neuregulin-1 signalling and antipsychotic treatment

Potential therapeutic targets in a schizophrenia candidate signalling pathway
  • Chao Deng
  • Bo Pan
  • Martin Engel
  • Xu-Feng Huang


Identifying the signalling pathways underlying the pathophysiology of schizophrenia is an essential step in the rational development of new antipsychotic drugs for this devastating disease. Evidence from genetic, transgenic and post-mortem studies have strongly supported neuregulin-1 (NRG1)–ErbB4 signalling as a schizophrenia susceptibility pathway. NRG1–ErbB4 signalling plays crucial roles in regulating neurodevelopment and neurotransmission, with implications for the pathophysiology of schizophrenia. Post-mortem studies have demonstrated altered NRG1–ErbB4 signalling in the brain of schizophrenia patients. Antipsychotic drugs have different effects on NRG1–ErbB4 signalling depending on treatment duration. Abnormal behaviours relevant to certain features of schizophrenia are displayed in NRG1/ErbB4 knockout mice or those with NRG1/ErbB4 over-expression, some of these abnormalities can be improved by antipsychotic treatment. NRG1–ErbB4 signalling has extensive interactions with the GABAergic, glutamatergic and dopaminergic neurotransmission systems that are involved in the pathophysiology of schizophrenia. These interactions provide a number of targets for the development of new antipsychotic drugs. Furthermore, the key interaction points between NRG1–ErbB4 signalling and other schizophrenia susceptibility genes may also potentially provide specific targets for new antipsychotic drugs. In general, identification of these targets in NRG1–ErbB4 signalling and interacting pathways will provide unique opportunities for the development of new generation antipsychotics with specific efficacy and fewer side effects.


Schizophrenia Neuregulin-1 ErbB4 receptor Antipsychotic Glutamatergic GABA Dopaminergic Drug target 



This study was supported by a University of Wollongong URC grant and an NHMRC project grant (APP1008473) to C. Deng, and the Schizophrenia Research Institute, Australia, utilising infrastructure funding from NSW Health. We would like to thank Dr Katrina Green for her critical reading of this manuscript.

Conflict of interest

The authors have no conflicts of interest to disclose.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Chao Deng
    • 1
    • 2
    • 3
    • 4
  • Bo Pan
    • 1
    • 2
  • Martin Engel
    • 2
    • 3
  • Xu-Feng Huang
    • 2
    • 3
  1. 1.Antipsychotic Research Laboratory, Illawarra Health and Medical Research InstituteUniversity of WollongongWollongongAustralia
  2. 2.Centre for Translational Neuroscience, School of Health Sciences, and Illawarra Health and Medical Research InstituteUniversity of WollongongWollongongAustralia
  3. 3.Schizophrenia Research InstituteDarlinghurstAustralia
  4. 4.Illawarra Health and Medical Research InstituteUniversity of WollongongWollongongAustralia

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