Many current pharmacological treatments for neuropsychiatric disorders, such as anxiety and depression, are limited by a delayed onset of therapeutic effect, adverse side effects, abuse potential or lack of efficacy in many patients. These off-target effects highlight the need to identify novel mechanisms and targets for treatment. Recently, modulation of Glo1 (glyoxalase I) activity was shown to regulate anxiety-like behaviour and seizure-susceptibility in mice. These effects are likely to be mediated through the regulation of MG (methylglyoxal) by Glo1, as MG acts as a competitive partial agonist at GABAA (γ-aminobutyric acid A) receptors. Thus modulation of MG by Glo1 represents a novel target for treatment. In the present article, we evaluate the therapeutic potential of indirectly modulating MG concentrations through Glo1 inhibitors for the treatment of neuropsychiatric disorders.
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April 2014
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Conference Article|
March 20 2014
Glo1 inhibitors for neuropsychiatric and anti-epileptic drug development
Katherine M.J. McMurray;
Katherine M.J. McMurray
*Committee on Neurobiology, University of Chicago, Chicago, IL 60637, USA
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Margaret G. Distler;
Margaret G. Distler
†Department of Pathology, University of Chicago, Chicago, IL 60637, U.S.A.
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Preetpal S. Sidhu;
Preetpal S. Sidhu
‡Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, U.S.A.
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James M. Cook;
James M. Cook
‡Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, U.S.A.
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Leggy A. Arnold;
Leggy A. Arnold
‡Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, U.S.A.
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Abraham A. Palmer;
Abraham A. Palmer
§Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL 60637, U.S.A.
∥Department of Human Genetics, University of Chicago, Chicago, IL 60637, U.S.A.
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Leigh D. Plant
Leigh D. Plant
1
¶Department of Biochemistry, Brandeis University, Waltham, MA 02453, U.S.A.
1To whom correspondence should be addressed (emailldplant@brandeis.edu).
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Publisher: Portland Press Ltd
Received:
January 20 2014
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2014 Biochemical Society
2014
Biochem Soc Trans (2014) 42 (2): 461–467.
Article history
Received:
January 20 2014
Citation
Katherine M.J. McMurray, Margaret G. Distler, Preetpal S. Sidhu, James M. Cook, Leggy A. Arnold, Abraham A. Palmer, Leigh D. Plant; Glo1 inhibitors for neuropsychiatric and anti-epileptic drug development. Biochem Soc Trans 1 April 2014; 42 (2): 461–467. doi: https://doi.org/10.1042/BST20140027
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