A study of galectin-1 as a possible therapeutic agent for amyotrophic lateral sclerosis

Galectin-1 作为肌萎缩侧索硬化症可能治疗剂的研究

• 批准号: 13670629
• 负责人: KATO Takeo
• 金额: $ 1.98万
• 依托单位: Yamagata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670629/
• 关键词: amyotrophic lateral sclerosis; galectin-1; motor neuron disease; oxidized galectin-1; reduced galectin-1

Background and purposeAbnormal accumulation of neurofilaments in motor neurons is a characteristic pathological finding in amyotrophic lateral sclerosis (ALS). Recently we revealed that oxidized galectin-1, which has axonal regeneration-enhancing activity, accumulates in the neurofilamentous lesions in ALS. The objective of this study was to investigate whether oxidized galectin-1 has a beneficial effect on ALS.MethodsOxidized recombinant human galectin-1 (rhGAL-1/ox) or physiological saline was injected into the left gastrocnemius muscle of transgenic mice with a mutant SOD1 (H46R), an animal model of ALS.ResultsAdministration of rhGAL-1/ox to the mice delayed the onset of motor dysfunction and prolonged the life of the mice and the duration of their illness. Motor neurons of the lumbar cord were more preserved in the mice injected with rhGAL-1/ox than in those injected with physiological saline.ConclusionThe study suggests that rhGal-1/ox administration could be a new therapeutic strategy for ALS.

运动神经元中神经丝的异常堆积是肌萎缩侧索硬化症(ALS)的典型病理表现。最近我们发现具有轴突再生促进活性的氧化半乳糖凝集素-1积聚在ALS的神经丝状病变中。方法将氧化重组人Galectin-1(rhGAL-1/OX)或生理盐水注入ALS动物模型--突变型SOD1(H46R)转基因小鼠的左侧腓肠肌，观察其对ALS的影响。注射rhGAL-1/OX的小鼠腰髓运动神经元较注射生理盐水的小鼠保存得更好。结论注射rhGal-1/OX有望成为治疗ALS的新策略。

项目成果

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Tobisawa S：“与家族性肌萎缩侧索硬化症相关的突变型 SOD1（而非野生型 SOD1）会在 COS7 细胞和转基因小鼠中诱导 ER 应激。”Biochem Biophys Res Commun。

Wada M, (他4名), Kato T: "Decreased galectin-1 immunoreactivity of the skin in amyotrophic lateral sclerosis"J. Neurul. Sci.. (in press).

Wada M，（其他 4 名），Kato T：“肌萎缩侧索硬化症中皮肤半乳糖凝集素 1 免疫反应性降低”J. Neurul。

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Kikuchi K：“proSAAS（一种粒蛋白样神经内分泌肽前体）的 N 末端片段与皮克氏病中的 tau 蛋白内含物有关。”Biochem Biophys Res Commun。

Kato T: "Galectin-1 is a component of neurofilamentous lesions in sporadic and familial amyotrophic lateral sclerosis."Biochem Biophys Res Commun. 282. 166-172 (2001)

Kato T：“Galectin-1 是散发性和家族性肌萎缩侧索硬化症中神经丝病变的一个组成部分。”Biochem Biophys Res Commun。