Zhang Zhong-Hao, Cao Xian-Chun, Peng Jia-Ying, Huang Shao-Ling, Chen Chen, Jia Shi-Zheng, Ni Jia-Zuan, Song Guo-Li
Shenzhen Key Laboratory of Marine Bioresources and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518000, China.
Shenzhen Bay Laboratory, Shenzhen 518000, China.
Antioxidants (Basel). 2022 Apr 24;11(5):829. doi: 10.3390/antiox11050829.
Aberrant lipid metabolism is reported to be closely related to the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD). Selenium (Se) and folate are two ideal and safe nutritional supplements, whose biological effects include regulating redox and homocysteine (Hcy) homeostasis in vivo. Here, to achieve effective multitarget therapy for AD, we combined Se and folic acid in a co-supplementation regimen (Se-FA) to study the therapeutic potential and exact mechanism in two transgenic mouse models of AD (APP/Tau/PSEN and APP/PS1). In addition to a reduction in Aβ generation and tau hyperphosphorylation, a restoration of synaptic plasticity and cognitive ability was observed in AD mice upon Se-FA administration. Importantly, by using untargeted metabolomics, we found that these improvements were dependent on the modulation of brain lipid metabolism, which may be associated with an antioxidant effect and the promotion of Hcy metabolism. Thus, from mechanism to effects, this study systematically investigated Se-FA as an intervention for AD, providing important mechanistic insights to inform its potential use in clinical trials.
据报道，异常的脂质代谢与神经退行性疾病（如阿尔茨海默病，AD）的发病机制密切相关。硒（Se）和叶酸是两种理想且安全的营养补充剂，其生物学作用包括调节体内氧化还原和同型半胱氨酸（Hcy）稳态。在此，为实现对AD的有效多靶点治疗，我们将硒和叶酸联合进行共同补充方案（Se-FA），以研究其在两种AD转基因小鼠模型（APP/Tau/PSEN和APP/PS1）中的治疗潜力及确切机制。除了减少Aβ生成和tau过度磷酸化外，在给予Se-FA后，AD小鼠的突触可塑性和认知能力得到恢复。重要的是，通过非靶向代谢组学研究，我们发现这些改善依赖于对脑脂质代谢的调节，这可能与抗氧化作用和促进Hcy代谢有关。因此，本研究从机制到效应系统地研究了Se-FA作为AD干预措施的作用，为其在临床试验中的潜在应用提供了重要的机制性见解。
