American Journal of Psychiatry and Neuroscience

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The Development of Small Molecule Angiotensin IV-Based Analogs to Treat Depression

Received: 09 July 2015    Accepted: 27 July 2015    Published: 03 August 2015
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Abstract

Major depression is a common form of mental disorder affecting approximately 15% of the population at least once during lifetime. The etiology of depression is complex with potential contributions from central and peripheral systemic factors, and several CNS impacting diseases. Presently employed antidepressant medications are poorly responded to by upwards of 50% of patients and typically require weeks of treatment to be effective. Recent post-mortem brain scans indicate significant volume reductions in two limbic brain structures, the hippocampus and prefrontal cortex of depressed patients. These findings focus attention on hippocampal plasticity in the neuropathology of depression and the possible dysfunction of several important processes including neurogenesis, synaptogenesis, and contributions by neurotrophic growth factors. The hepatocyte growth factor (HGF)/c-Met receptor system is a powerful mediator of synaptogenesis and neurogenesis, and if adequately activated may serve to counter the neuropathology of depression. The brain renin-angiotensin system (RAS) interacts with the HGF/c-Met system and plays a major role in responding to stress and the pathophysiology of depression. We have developed an angiotensin IV-based small molecule designed to activate the HGF/c-Met receptor system in order to provide neuroprotection, synaptogenesis, and neurogenesis in the hippocampus and prefrontal cortex. This analog may be efficacious in treating the neuropathology of depression.

DOI 10.11648/j.ajpn.20150305.11
Published in American Journal of Psychiatry and Neuroscience (Volume 3, Issue 5, September 2015)
Page(s) 77-89
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Depression, Angiotensin II, Angiotensin IV, AT4 Receptor, Hepatocyte Growth Factor, C-Met Receptor, Dihexa

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  • Departments of Psychology, Integrative Physiology and Neuroscience, and Program in Biotechnology, Washington State University, Pullman, USA; M3 Biotechnology, Inc., Seattle, USA

  • Departments of Psychology, Integrative Physiology and Neuroscience, and Program in Biotechnology, Washington State University, Pullman, USA; M3 Biotechnology, Inc., Seattle, USA

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    John W. Wright, Joseph W. Harding. (2015). The Development of Small Molecule Angiotensin IV-Based Analogs to Treat Depression. American Journal of Psychiatry and Neuroscience, 3(5), 77-89. https://doi.org/10.11648/j.ajpn.20150305.11

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    John W. Wright; Joseph W. Harding. The Development of Small Molecule Angiotensin IV-Based Analogs to Treat Depression. Am. J. Psychiatry Neurosci. 2015, 3(5), 77-89. doi: 10.11648/j.ajpn.20150305.11

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    John W. Wright, Joseph W. Harding. The Development of Small Molecule Angiotensin IV-Based Analogs to Treat Depression. Am J Psychiatry Neurosci. 2015;3(5):77-89. doi: 10.11648/j.ajpn.20150305.11

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  • @article{10.11648/j.ajpn.20150305.11,
      author = {John W. Wright and Joseph W. Harding},
      title = {The Development of Small Molecule Angiotensin IV-Based Analogs to Treat Depression},
      journal = {American Journal of Psychiatry and Neuroscience},
      volume = {3},
      number = {5},
      pages = {77-89},
      doi = {10.11648/j.ajpn.20150305.11},
      url = {https://doi.org/10.11648/j.ajpn.20150305.11},
      eprint = {https://download.sciencepg.com/pdf/10.11648.j.ajpn.20150305.11},
      abstract = {Major depression is a common form of mental disorder affecting approximately 15% of the population at least once during lifetime. The etiology of depression is complex with potential contributions from central and peripheral systemic factors, and several CNS impacting diseases. Presently employed antidepressant medications are poorly responded to by upwards of 50% of patients and typically require weeks of treatment to be effective. Recent post-mortem brain scans indicate significant volume reductions in two limbic brain structures, the hippocampus and prefrontal cortex of depressed patients. These findings focus attention on hippocampal plasticity in the neuropathology of depression and the possible dysfunction of several important processes including neurogenesis, synaptogenesis, and contributions by neurotrophic growth factors. The hepatocyte growth factor (HGF)/c-Met receptor system is a powerful mediator of synaptogenesis and neurogenesis, and if adequately activated may serve to counter the neuropathology of depression. The brain renin-angiotensin system (RAS) interacts with the HGF/c-Met system and plays a major role in responding to stress and the pathophysiology of depression. We have developed an angiotensin IV-based small molecule designed to activate the HGF/c-Met receptor system in order to provide neuroprotection, synaptogenesis, and neurogenesis in the hippocampus and prefrontal cortex. This analog may be efficacious in treating the neuropathology of depression.},
     year = {2015}
    }
    

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  • TY  - JOUR
    T1  - The Development of Small Molecule Angiotensin IV-Based Analogs to Treat Depression
    AU  - John W. Wright
    AU  - Joseph W. Harding
    Y1  - 2015/08/03
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    DO  - 10.11648/j.ajpn.20150305.11
    T2  - American Journal of Psychiatry and Neuroscience
    JF  - American Journal of Psychiatry and Neuroscience
    JO  - American Journal of Psychiatry and Neuroscience
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    PB  - Science Publishing Group
    SN  - 2330-426X
    UR  - https://doi.org/10.11648/j.ajpn.20150305.11
    AB  - Major depression is a common form of mental disorder affecting approximately 15% of the population at least once during lifetime. The etiology of depression is complex with potential contributions from central and peripheral systemic factors, and several CNS impacting diseases. Presently employed antidepressant medications are poorly responded to by upwards of 50% of patients and typically require weeks of treatment to be effective. Recent post-mortem brain scans indicate significant volume reductions in two limbic brain structures, the hippocampus and prefrontal cortex of depressed patients. These findings focus attention on hippocampal plasticity in the neuropathology of depression and the possible dysfunction of several important processes including neurogenesis, synaptogenesis, and contributions by neurotrophic growth factors. The hepatocyte growth factor (HGF)/c-Met receptor system is a powerful mediator of synaptogenesis and neurogenesis, and if adequately activated may serve to counter the neuropathology of depression. The brain renin-angiotensin system (RAS) interacts with the HGF/c-Met system and plays a major role in responding to stress and the pathophysiology of depression. We have developed an angiotensin IV-based small molecule designed to activate the HGF/c-Met receptor system in order to provide neuroprotection, synaptogenesis, and neurogenesis in the hippocampus and prefrontal cortex. This analog may be efficacious in treating the neuropathology of depression.
    VL  - 3
    IS  - 5
    ER  - 

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