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与年龄匹配的对照组相比,阿尔茨海默病患者淋巴母细胞系中牛磺酸转运体表达降低:有治疗意义吗?

Reduced Taurine Transporter Expression in Lymphoblastoid Cell Lines From Alzheimer's Disease Patients Compared With Age-Matched Controls: Therapeutic Implications?

作者信息

Gavriel Yuval, Voinsky Irena, Klin Hana, Squassina Alessio, Gurwitz David

机构信息

Department of Human Molecular Genetics and Biochemistry, Gray Faculty of Health and Medical Sciences, Tel Aviv University, Tel Aviv, Israel.

Department of Cell and Developmental Biology, Gray Faculty of Health and Medical Sciences, Tel Aviv University, Tel Aviv, Israel.

出版信息

Drug Dev Res. 2025 Aug;86(5):e70124. doi: 10.1002/ddr.70124.

Abstract

Taurine is an atypical amino acid that cannot form peptide bonds and thus does not take place in building proteins. Yet, taurine takes part in regulating many cell functions, including cell osmolarity and volume, mitochondrial function, membrane ion channels and neuronal activity, and cell survival. Taurine is synthesized by the liver, and available from consumption of meat and fish, but not plants. It has millimolar concentrations in the brain, skeletal muscle, blood, heart, retina, and other tissues. Taurine is transported from the liver (following synthesis) or the intestine (following consumption) to blood by the taurine transporter, encoded in humans by SLC6A6. A recent study reported that blood taurine declines dramatically in aged individuals. Several studies indicated that dietary taurine slows cognitive decline in Alzheimer's disease (AD) model mice. We therefore measured SLC6A6 mRNA expression in human lymphoblastoid cell lines (LCLs) from AD patients and age-matched controls and observed 2.8-fold lower expression in AD LCLs (p = 0.0005). Additionally, glutathione peroxidase 1 (GPX1), a key free-radical scavenging selenoenzyme, had reduced mRNA expression in LCLs from AD patients compared with controls. Our observations suggest that reduced taurine transporter expression may contribute to AD pathogenesis and that dietary taurine might be beneficial for slowing disease progression in early-stage AD. Clinical trials with dietary taurine supplementation of individuals with mild cognitive impairment (MCI) or early-stage AD are required to assess its tentative therapeutic potential.

摘要

牛磺酸是一种非典型氨基酸,它不能形成肽键,因此不参与蛋白质的合成。然而,牛磺酸参与调节许多细胞功能,包括细胞渗透压和体积、线粒体功能、膜离子通道和神经元活动以及细胞存活。牛磺酸由肝脏合成,可从肉类和鱼类中获取,但植物中不含。它在大脑、骨骼肌、血液、心脏、视网膜和其他组织中的浓度为毫摩尔级。牛磺酸通过牛磺酸转运体从肝脏(合成后)或肠道(摄入后)转运到血液中,在人类中由SLC6A6编码。最近的一项研究报告称,老年人血液中的牛磺酸含量会大幅下降。多项研究表明,饮食中的牛磺酸可减缓阿尔茨海默病(AD)模型小鼠的认知衰退。因此,我们测量了AD患者和年龄匹配的对照组的人淋巴母细胞系(LCLs)中SLC6A6 mRNA的表达,发现AD-LCLs中的表达降低了2.8倍(p = 0.0005)。此外,与对照组相比,AD患者LCLs中关键的自由基清除硒酶谷胱甘肽过氧化物酶1(GPX1)的mRNA表达降低。我们的观察结果表明,牛磺酸转运体表达降低可能导致AD发病机制,饮食中的牛磺酸可能有助于减缓早期AD的疾病进展。需要对轻度认知障碍(MCI)或早期AD患者进行补充牛磺酸的临床试验,以评估其初步治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c719/12239548/c5138d42cd4b/DDR-86-e70124-g004.jpg

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