Wang Cheng-Cheng, Kong Jing-Ya, Xue Chang-Hu, Zhang Tian-Tian, Wang Yu-Ming
College of Food Science and Engineering, Ocean University of China, Qingdao, Shandong Province, 266404, P. R. China.
Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, Shandong Province, 266237, P. R. China.
Mol Nutr Food Res. 2023 Apr;67(8):e2200825. doi: 10.1002/mnfr.202200825. Epub 2023 Mar 8.
Blood-brain barrier (BBB) impairment is related to the development of Alzheimer's disease (AD), which is dependent not only on tight junction but also on transcytosis of brain endothelial cells (BECs) in the BBB. Aging induces the decrease of ligand-specific receptor-mediated transcytosis (RMT) and the increase of non-specific caveolar transcytosis in BECs, which lead to the entry into parenchyma of neurotoxic proteins and the smaller therapeutic index in central nervous system drug delivery, further provoking neurodegenerative disease. A previous study suggests that sea-derived Antarctic krill oil (AKO) exhibits synergistic effects with land-derived nobiletin (NOB) and theanine (THE) on ameliorating memory and cognitive deficiency in SAMP8 mice. However, it is still unclear whether BBB change is involved. Hence, the effects of AKO combined with NOB and THE on aging-induced BBB impairment, including tight junction between BECs, ligand-specific RMT, and non-specific caveolar transcytosis in BECs, are investigated. The results suggest that AKO exhibits synergistic effects with NOB and THE on regulating ligand-specific RMT in BBB by inhibiting alkaline phosphatase (ALPL). The study provides a potential strategy candidate or targeted dietary patterns to prevent and treat AD by improving the BBB function.
血脑屏障（BBB）损伤与阿尔茨海默病（AD）的发展有关，这不仅取决于紧密连接，还取决于血脑屏障中脑内皮细胞（BECs）的转胞吞作用。衰老导致BECs中配体特异性受体介导的转胞吞作用（RMT）减少和非特异性小窝转胞吞作用增加，这导致神经毒性蛋白进入实质以及中枢神经系统药物递送中的治疗指数降低，进而引发神经退行性疾病。先前的一项研究表明，海洋来源的南极磷虾油（AKO）与陆地来源的诺米林（NOB）和茶氨酸（THE）对改善SAMP8小鼠的记忆和认知缺陷具有协同作用。然而，血脑屏障的变化是否涉及其中仍不清楚。因此，研究了AKO与NOB和THE联合使用对衰老诱导的血脑屏障损伤的影响，包括BECs之间的紧密连接、配体特异性RMT以及BECs中的非特异性小窝转胞吞作用。结果表明，AKO通过抑制碱性磷酸酶（ALPL）与NOB和THE在调节血脑屏障中配体特异性RMT方面具有协同作用。该研究为通过改善血脑屏障功能预防和治疗AD提供了一种潜在的策略候选物或靶向饮食模式。
