Skalny Anatoly V, Aschner Michael, Santamaria Abel, Filippini Tommaso, Gritsenko Viktor A, Tizabi Yousef, Zhang Feng, Guo Xiong, Rocha Joao B T, Tinkov Alexey A
Laboratory of Ecobiomonitoring and Quality Control, Yaroslavl State University, Sovetskaya Str. 14, Yaroslavl, 150000, Russia.
Laboratory of Molecular Dietetics, IM Sechenov First Moscow State Medical University (Sechenov University), Bolshaya Pirogovskaya St., 2-4, Moscow, 119146, Russia.
Mol Neurobiol. 2025 Feb;62(2):1675-1692. doi: 10.1007/s12035-024-04343-w. Epub 2024 Jul 16.
The objective of the present review was to provide a timely update on the molecular mechanisms underlying the beneficial role of Se in Alzheimer's disease pathogenesis, and discuss the potential role of gut microbiota modulation in this neuroprotective effect. The existing data demonstrate that selenoproteins P, M, S, R, as well as glutathione peroxidases and thioredoxin reductases are involved in regulation of Aβ formation and aggregation, tau phosphorylation and neurofibrillary tangles formation, as well as mitigate the neurotoxic effects of Aβ and phospho-tau. Correspondingly, supplementation with various forms of Se in cellular and animal models of AD was shown to reduce Aβ formation, tau phosphorylation, reverse the decline in brain antioxidant levels, inhibit neuronal oxidative stress and proinflammatory cytokine production, improve synaptic plasticity and neurogenesis, altogether resulting in improved cognitive functions. In addition, most recent findings demonstrate that these neuroprotective effects are associated with Se-induced modulation of gut microbiota. In animal models of AD, Se supplementation was shown to improve gut microbiota biodiversity with a trend to increased relative abundance of Lactobacillus, Bifidobacterium, and Desulfivibrio, while reducing that of Lachnospiracea_NK4A136, Rikenella, and Helicobacter. Moreover, the relative abundance of Se-affected taxa was significantly associated with Aβ accumulation, tau phosphorylation, neuronal oxidative stress, and neuroinflammation, indicative of the potential role of gut microbiota to mediate the neuroprotective effects of Se in AD. Hypothetically, modulation of gut microbiota along with Se supplementation may improve the efficiency of the latter in AD, although further detailed laboratory and clinical studies are required.
本综述的目的是及时更新关于硒在阿尔茨海默病发病机制中的有益作用的分子机制，并讨论肠道微生物群调节在这种神经保护作用中的潜在作用。现有数据表明，硒蛋白P、M、S、R以及谷胱甘肽过氧化物酶和硫氧还蛋白还原酶参与了β淀粉样蛋白（Aβ）形成和聚集、tau蛋白磷酸化和神经原纤维缠结形成的调节，以及减轻Aβ和磷酸化tau的神经毒性作用。相应地，在AD的细胞和动物模型中补充各种形式的硒可减少Aβ形成、tau蛋白磷酸化，逆转脑抗氧化水平的下降，抑制神经元氧化应激和促炎细胞因子的产生，改善突触可塑性和神经发生，从而改善认知功能。此外，最新研究结果表明，这些神经保护作用与硒诱导的肠道微生物群调节有关。在AD动物模型中，补充硒可改善肠道微生物群的生物多样性，乳酸杆菌、双歧杆菌和脱硫弧菌的相对丰度有增加趋势，而毛螺菌科_NK4A136、理研菌属和幽门螺杆菌的相对丰度则降低。此外，受硒影响的分类群的相对丰度与Aβ积累、tau蛋白磷酸化、神经元氧化应激和神经炎症显著相关，表明肠道微生物群可能在介导硒在AD中的神经保护作用。假设，调节肠道微生物群并补充硒可能会提高后者在AD中的效率，不过还需要进一步详细的实验室和临床研究。
