Glo1 inhibitors for neuropsychiatric and anti-epileptic drug development. Biochem Soc Trans 2014 Apr;42(2):461-7
Date
03/22/2014Pubmed ID
24646261Pubmed Central ID
PMC4036232DOI
10.1042/BST20140027Scopus ID
2-s2.0-84896922293 (requires institutional sign-in at Scopus site) 22 CitationsAbstract
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.
Author List
McMurray KM, Distler MG, Sidhu PS, Cook JM, Arnold LA, Palmer AA, Plant LDAuthors
Alexander (Leggy) Arnold PhD Professor in the Chemistry & Biochemistry department at University of Wisconsin - MilwaukeeJames M. Cook PhD University Distinguished Professor in the Chemistry and Biochemistry department at University of Wisconsin - Milwaukee
MESH terms used to index this publication - Major topics in bold
AnimalsAnticonvulsants
Humans
Lactoylglutathione Lyase
Pyruvaldehyde
Seizures
