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.
Glo1 inhibitors for neuropsychiatric and anti-epileptic drug development
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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