title: Therapeutic effects of methionine sulfoximine in multiple diseases include and extend beyond inhibition of glutamine synthetase.
abstract: Methionine sulfoximine (MSO), a well-characterized inhibitor of glutamine synthetase, displays significant therapeutic benefits in animal models for several human diseases. This amino acid might therefore be a viable candidate for drug development to treat diseases for which there are few effective therapies. Areas covered: We describe the effects of MSO on brain swelling occurring in overt hepatic encephalopathy resulting from liver failure, the effects of MSO on excitotoxic damage involved in amyotrophic lateral sclerosis (ALS) or resulting from stroke, and the effects of MSO on a model for an inflammatory immune response involved in a range of diseases. We conclude that these results imply the existence of another therapeutic target for MSO in addition to glutamine synthetase. Expert opinion: We summarize the various diseases for which MSO treatment might be a candidate for drug development. We discuss why MSO has limited enthusiasm in the scientific and medical communities for use in humans, with a rebuttal to those negative opinions. And we conclude that MSO should be considered a candidate drug to treat brain swelling involved in overt hepatic encephalopathy and diseases involving an inflammatory immune response.
authors.affiliation: a Department of Biochemistry and Molecular Biology , Wayne State University School of Medicine , Detroit , MI , USA.
authors.forename: William S A
authors.initials: WS
authors.lastname: Brusilow
authors.affiliation: a Department of Biochemistry and Molecular Biology , Wayne State University School of Medicine , Detroit , MI , USA.
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Peters
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy / Q000503:physiopathology; D000818:Animals; D001929:Brain Edema / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D015195:Drug Design; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D006501:Hepatic Encephalopathy / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D008717:Methionine Sulfoximine / Q000494:pharmacology*; D058990:Molecular Targeted Therapy; D020521:Stroke / Q000188:drug therapy / Q000503:physiopathology
chemical_list: D008717:Methionine Sulfoximine; D005974:Glutamate-Ammonia Ligase
keywords: ALS; Glutamine synthetase; hepatic encephalopathy; inflammation; methionine sulfoximine