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S-Adenosylmethionine Alleviates Amyloid-β-Induced Neural Injury by Enhancing Trans-Sulfuration Pathway Activity in Astrocytes.
Journal of Alzheimer’s Disease ( IF 4 ) Pub Date : 2020-06-24 , DOI: 10.3233/jad-200103
Xinkun Wan 1 , Bin Ma 1 , Xiaoxuan Wang 1 , Chenjia Guo 1 , Jing Sun 1 , Jing Cui 1 , Liang Li 1
Affiliation  

Background:Glutathione (GSH) is an important endogenous antioxidant protecting cells from oxidative injury. Cysteine (Cys), the substrate limiting the production of GSH, is mainly generated from the trans-sulfuration pathway. S-adenosylmethionine (SAM) is a critical molecule produced in the methionine cycle and can be utilized by the trans-sulfuration pathway. Reductions in GSH and SAM as well as dysfunction in the trans-sulfuration pathway have been documented in the brains of Alzheimer’s disease (AD) patients. Our previous in vivo study revealed that SAM administration attenuated oxidative stress induced by amyloid-β (Aβ) through the enhancement of GSH. Objective:To investigate the effect of Aβ-induced oxidative stress on the trans-sulfuration pathway in astrocytes and neurons, respectively, and the protective effect of SAM on neurons. Methods:APP/PS1 transgenic mice and the primary cultured astrocytes, neurons, and HT22 cells were used in the current study. Results:SAM could rescue the low trans-sulfuration pathway activity induced by Aβ only in astrocytes, accompanying with increasing levels of Cys and GSH. The decrease of cellular viability of neurons caused by Aβ was greatly reversed when co-cultured with astrocytes with SAM intervention. Meanwhile, SAM improved cognitive performance in APP/PS1 mice. Conclusion:In terms of astrocyte protection from oxidative stress, SAM might be a potent antioxidant in the therapy of AD patients.

中文翻译:

S-腺苷甲硫氨酸可通过增强星形胶质细胞中的跨硫途径来减轻淀粉样蛋白-β引起的神经损伤。

背景:谷胱甘肽(GSH)是一种重要的内源性抗氧化剂,可保护细胞免受氧化损伤。半胱氨酸(Cys)是限制GSH生成的底物,主要是由反硫化途径产生的。S-腺苷甲硫氨酸(SAM)是在甲硫氨酸循环中产生的关键分子,可以被反硫途径利用。在阿尔茨海默氏病(AD)患者的大脑中,GSH和SAM的降低以及转硫途径的功能障碍已被证明。我们以前的体内研究表明,SAM的给药通过增强GSH来减轻淀粉样蛋白-β(Aβ)诱导的氧化应激。目的:研究Aβ诱导的氧化应激分别对星形胶质细胞和神经元的反硫酸化途径的影响,以及SAM对神经元的保护作用。方法:APP / PS1转基因小鼠和原代培养的星形胶质细胞,神经元和HT22细胞用于当前研究。结果:SAM只能挽救星形胶质细胞中Aβ诱导的低转硫途径活性,并伴有Cys和GSH水平升高。当与星形胶质细胞在SAM干预下共培养时,由Aβ引起的神经元细胞活力的下降被大大逆转。同时,SAM改善了APP / PS1小鼠的认知能力。结论:就星形胶质细胞免受氧化应激的保护而言,SAM可能是治疗AD患者的有效抗氧化剂。伴随着Cys和GSH水平的升高。当与星形胶质细胞在SAM干预下共培养时,由Aβ引起的神经元细胞活力的下降被大大逆转。同时,SAM改善了APP / PS1小鼠的认知能力。结论:就星形胶质细胞免受氧化应激的保护而言,SAM可能是治疗AD患者的有效抗氧化剂。伴随着Cys和GSH水平的升高。当与星形胶质细胞在SAM干预下共培养时,由Aβ引起的神经元细胞活力的下降被大大逆转。同时,SAM改善了APP / PS1小鼠的认知能力。结论:就星形胶质细胞免受氧化应激的保护而言,SAM可能是治疗AD患者的有效抗氧化剂。
更新日期:2020-06-30
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