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鉴定可延长SOD1 G93A小鼠寿命的蛋氨酸亚砜亚胺异构体。

Identification of the isomer of methionine sulfoximine that extends the lifespan of the SOD1 G93A mouse.

作者信息

Brusilow William S A

机构信息

Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Scott Hall, 540 E. Canfield Ave., Detroit, MI 48201, United States.

出版信息

Neurosci Lett. 2017 Apr 24;647:165-167. doi: 10.1016/j.neulet.2017.03.029. Epub 2017 Mar 18.

Abstract

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.

摘要

在先前的研究中,蛋氨酸亚砜亚胺(MSO)显著延长了肌萎缩侧索硬化症(ALS)的SOD1 G93A小鼠模型的寿命。那些研究使用的是市售的MSO,它是LS和LR非对映异构体的外消旋混合物,因此哪种异构体具有治疗作用的问题仍未得到解答。在本研究中,我们对两种纯化的异构体进行了测试,结果表明,LS异构体(一种已明确的谷氨酰胺合成酶抑制剂)可延长这些小鼠的寿命,而LR异构体(尚无已知活性)则不能。

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