Lipid Biofunction Section, Faculty of Advanced Life Science, Hokkaido University, Kita-21, Nishi-11, Kita-ku, Sapporo, 001-0021, Japan.
Glycoconj J. 2022 Oct;39(5):613-618. doi: 10.1007/s10719-022-10066-8. Epub 2022 Aug 3.
Glycosphingolipids (GSLs) are a specialized class of membrane lipids composed of a ceramide and a carbohydrate head group. GSLs are localized in cell membranes and were recently found to be enriched in the membrane of neuron-derived exosomes, which are a type of extracellular vesicle. Our studies demonstrated that exosomal GSLs may be associated with the amyloid-ß (Aß) peptide, a principal agent of Alzheimer's disease (AD), and act to clear Aß by transporting Aß into brain phagocytic microglia. In this review, we summarize and discuss the function of exosomal GSLs in Aß homeostasis in AD pathology. Improvement in Aß clearance is a potent strategy for AD prevention and therapy. Dietary glucosylceramides (GlcCer) isolated from plants are absorbed into the body as various metabolites, including ceramides. Our recent work demonstrated that dietary GlcCer accelerates neuronal exosome production, which facilitates Aß clearance in mice. Furthermore, studies of AD model mice and human clinical trials have found that oral administration of plant-type GlcCer attenuates the Aß burden in the brain. We also introduce the development of plant-type GlcCer as functional food materials to prevent AD.
糖脂（Glycosphingolipids，GSLs）是一类特殊的膜脂，由神经酰胺和碳水化合物头部基团组成。GSLs 位于细胞膜中，最近发现其在神经元衍生的外泌体（一种细胞外囊泡）的膜中丰富存在。我们的研究表明，外泌体 GSLs 可能与淀粉样蛋白-β（amyloid-β，Aβ）肽有关，Aβ肽是阿尔茨海默病（Alzheimer's disease，AD）的主要致病因子，并通过将 Aβ 转运到大脑吞噬性小胶质细胞中，从而发挥清除 Aβ 的作用。在这篇综述中，我们总结并讨论了外泌体 GSLs 在 AD 病理中 Aβ 稳态中的作用。改善 Aβ 清除是预防和治疗 AD 的有效策略。从植物中分离出的神经酰胺葡萄糖苷（Glucosylceramides，GlcCer）被人体吸收为各种代谢物，包括神经酰胺。我们最近的工作表明，饮食中的 GlcCer 可加速神经元外泌体的产生，从而促进小鼠 Aβ 的清除。此外，AD 模型小鼠和人类临床试验的研究发现，植物型 GlcCer 的口服给药可减轻大脑中的 Aβ 负担。我们还介绍了植物型 GlcCer 作为预防 AD 的功能性食品材料的开发。
