Se-Methylselenocysteine (SMC) Improves Cognitive Deficits by Attenuating Synaptic and Metabolic Abnormalities in Alzheimer's Mice Model: A Proteomic Study
Se-Methylselenocysteine (SMC) Improves Cognitive Deficits by Attenuating Synaptic and Metabolic Abnormalities in Alzheimer's Mice Model: A Proteomic Study
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Se-甲基硒代半胱氨酸 (SMC) 通过减轻阿尔茨海默病小鼠模型的突触和代谢异常来改善认知缺陷：一项蛋白质组学研究
DOI：
10.1021/acschemneuro.0c00549
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发表时间：
2021-03-09
影响因子：
5
通讯作者：
Shen, Liming
中科院分区：
文献类型：
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作者：
Du, Xiubo;Shi, Qingqing;Shen, Liming
Se-甲基硒代半胱氨酸 (SMC) 是富硒 (Se) 植物中的主要硒化合物，已被发现可改善阿尔茨海默病三重转基因小鼠模型（3 x Tg-AD 小鼠）的神经病理学和认知缺陷。为了探索潜在的分子机制，本研究旨在阐明 SMC 处理的 3 x Tg-AD 小鼠皮质中的蛋白质变化。补充 SMC 后，蛋白质组学分析显示，3 x Tg-AD 小鼠与野生型（AD/WT 组）、SMC 处理的 AD 小鼠与 AD（AD + SMC/AD）和 AD + SMC/WT 组之间分别有 181、271 和 41 个蛋白质被鉴定为差异表达蛋白（DEP）。其中，患病组中有138种蛋白质被SMC治疗逆转。 AD/WT组和AD+SMC/AD组的DEP主要与代谢、突触和抗氧化蛋白有关，而其水平在AD小鼠中降低，但在SMC治疗后上调。此外，我们发现 AD 小鼠大脑中 ATP 水平降低并破坏了突触结构，这些情况在 SMC 治疗后得到显着改善。我们的研究表明，能量代谢紊乱、氨基酸代谢异常、突触功能障碍和氧化应激可能是AD的关键致病现象。 SMC逆转与其相关的蛋白质的表达，这可能是其干预AD的主要机制。
Se-methylselenocysteine (SMC) is a major selenocompound in selenium (Se) enriched plants and has been found to ameliorate neuropathology and cognitive deficits in triple-transgenic mice model of Alzheimer's disease (3 x Tg-AD mice). To explore the underlying molecular mechanisms, the present study is designed to elucidate the protein changes in the cortex of SMC-treated 3 x Tg-AD mice. After SMC supplementation, proteomic analysis revealed that 181, 271, and 41 proteins were identified as differentially expressed proteins (DEPs) between 3 x Tg-AD mice vs wild type (AD/WT group), SMC-treated AD mice vs AD (AD + SMC/AD), and AD + SMC/WT group, respectively. Among these, 138 proteins in the diseased group were reversed by SMC treatment. The DEPs in AD/WT group and AD + SMC/AD group were mainly related to metabolism, synapses, and antioxidant proteins, while their levels were decreased in AD mice but up-regulated after treating with SMC. In addition, we found reduced ATP levels and destroyed synaptic structures in the AD mice brains, which were significantly ameliorated upon SMC treatment. Our study suggests that energy metabolism disorders, abnormal amino acid metabolism, synaptic dysfunction, and oxidative stress may be the key pathogenic phenomena of AD. SMC reversed the expression of proteins associated with them, which might be the main mechanism of its intervention in AD.