title: Glo1 inhibitors for neuropsychiatric and anti-epileptic drug development.
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.
authors.affiliation: *Committee on Neurobiology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Katherine M J
authors.initials: KM
authors.lastname: McMurray
authors.affiliation: †Department of Pathology, University of Chicago, Chicago, IL 60637, U.S.A.
authors.forename: Margaret G
authors.initials: MG
authors.lastname: Distler
authors.affiliation: ‡Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, U.S.A.
authors.forename: Preetpal S
authors.initials: PS
authors.lastname: Sidhu
authors.affiliation: ‡Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, U.S.A.
authors.forename: James M
authors.initials: JM
authors.lastname: Cook
authors.affiliation: ‡Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, U.S.A.
authors.forename: Leggy A
authors.initials: LA
authors.lastname: Arnold
authors.forename: Abraham A
authors.initials: AA
authors.lastname: Palmer
authors.affiliation: ¶Department of Biochemistry, Brandeis University, Waltham, MA 02453, U.S.A.
authors.forename: Leigh D
authors.initials: LD
authors.lastname: Plant
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000037:antagonists & inhibitors*; D011765:Pyruvaldehyde / Q000378:metabolism; D012640:Seizures / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D011765:Pyruvaldehyde; D007791:Lactoylglutathione Lyase