Identification of the isomer of methionine sulfoximine that extends the lifespan of the SOD1 G93A mouse.
In previous studies methionine sulfoximine (MSO) significantly extended the lifespan of the SOD1 G93A mouse model for ALS. Those studies used commercially available MSO, which is a racemic mixture of the LS and LR diastereomers, leaving unanswered the question of which isomer was responsible for the therapeutic effects. In this study we tested both purified isomers and showed that the LS isomer, a well-characterized inhibitor of glutamine synthetase, extends the lifespan of these mice, but the LR isomer, which has no known activity, does not.
Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Scott Hall, 540 E. Canfield Ave., Detroit, MI 48201, United States. Electronic address: aa2801@wayne.edu.
William S A
WS
Brusilow
D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D000818:Animals; D005974:Glutamate-Ammonia Ligase / Q000037:antagonists & inhibitors*; D008136:Longevity / Q000187:drug effects; D008717:Methionine Sulfoximine / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D008822:Mice, Transgenic; D013237:Stereoisomerism; D000072105:Superoxide Dismutase-1 / Q000235:genetics*; D015996:Survival Rate
D008717:Methionine Sulfoximine; C000606291:Sod1 protein, mouse; D000072105:Superoxide Dismutase-1; D005974:Glutamate-Ammonia Ligase
ALS; Excitotoxicity; Glutamine synthetase; Methionine sulfoximine; SOD1