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Relevance of Presynaptic Proteins to Neuropsychiatric Disorders

  • Chapter
Molecular Mechanisms of Synaptogenesis

1. Summary

Schizophrenia is a psychiatric disorder that likely arises from a complex series of interactions between genetic and environmental factors, resulting in altered neural connectivity. Consistent with this position, an extensive body of research has demonstrated that the molecular machinery that regulates synaptic activity is altered in post mortem brain tissue in schizophrenia. In particular, the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein synaptosomal-associated protein-25 (SNAP-25) and the SNARE-interacting proteins complexin I and II are implicated in the pathophysiology of this disorder. These proteins regulate synaptic neurotransmission and are important for plasticity-associated changes in the brain. Recent evidence from our laboratory has demonstrated that levels of these proteins are decreased in the hippocampus in schizophrenia, and importantly, these decreases are significantly associated with cognitive impairment. These findings represent the first description significantly linking synaptic proteins to cognitive function in schizophrenia. Preclinical studies provide evidence that SNAP-25 and complexins may be implicated in the pathophysiology of additional psychiatric and neurological disorders, as well as in the therapeutic efficacy of drugs used in the treatment of these disorders.

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Authors and Affiliations

  1. Department of Psychiatry, Center for Complex Disorders, University of British Columbia, Vancouver General Hospital Research Pavilion, 828 West 10th Avenue, Vancouver, BC, Canada, V5Z 1L8

    Alasdair M. Barr, Clint E. Young & William G. Honer

  2. Department of Neuropsychiatry, Kochi Medical School, Kochi, Japan

    Ken Sawada

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  1. Alasdair M. Barr
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  2. Clint E. Young
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  3. Ken Sawada
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  4. William G. Honer
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Editors and Affiliations

  1. University Medical Center Hamburg-Eppendorf, 52 Martinistrasse, Hamburg, 20246, Germany

    Alexander Dityatev

  2. University of British Columbia, 2255 Wesbrook Mall, Vancouver, British Columbia, Canada, V6T 2A1

    Alaa El-Husseini

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Barr, A.M., Young, C.E., Sawada, K., Honer, W.G. (2006). Relevance of Presynaptic Proteins to Neuropsychiatric Disorders. In: Dityatev, A., El-Husseini, A. (eds) Molecular Mechanisms of Synaptogenesis. Springer, Boston, MA . https://doi.org/10.1007/978-0-387-32562-0_27

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