Glo1 inhibitors for neuropsychiatric and anti-epileptic drug development

• Published in: Biochemical Society transactions Vol. 42; no. 2; p. 461
• Main Authors: McMurray, Katherine M J, Distler, Margaret G, Sidhu, Preetpal S, Cook, James M, Arnold, Leggy A, Palmer, Abraham A, Plant, Leigh D
• Format: Journal Article
• Language: English
• Published: England 01.04.2014
• Subjects: Animals; Anticonvulsants - therapeutic use; Humans; Lactoylglutathione Lyase - antagonists & inhibitors; Pyruvaldehyde - metabolism; Seizures - drug therapy; Seizures - metabolism
• ISSN: 1470-8752
• DOI: 10.1042/BST20140027

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.