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Biochem Soc Trans. 2014 Apr;42(2):461-7. doi: 10.1042/BST20140027.

Glo1 inhibitors for neuropsychiatric and anti-epileptic drug development.

Author information

1
*Committee on Neurobiology, University of Chicago, Chicago, IL 60637, USA.
2
†Department of Pathology, University of Chicago, Chicago, IL 60637, U.S.A.
3
‡Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, U.S.A.
4
¶Department of Biochemistry, Brandeis University, Waltham, MA 02453, U.S.A.

Abstract

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 GABA(A) (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.

PMID:
24646261
PMCID:
PMC4036232
DOI:
10.1042/BST20140027
[Indexed for MEDLINE]
Free PMC Article

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