Araújo Ana R, Castro Vânia I B, Reis Rui L, Pires Ricardo A
3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Portugal.
ICVS/3B's - PT Government Associate Laboratory, 4806-909 Braga/Guimarães, Portugal.
ACS Med Chem Lett. 2021 Mar 24;12(4):548-554. doi: 10.1021/acsmedchemlett.0c00350. eCollection 2021 Apr 8.
In Alzheimer's disease (AD), amyloid-β (Aβ) oligomers are considered key mediators of synaptic dysfunction and cognitive impairment. These unstable intermediate Aβ species can interfere with different cellular organelles, leading to neuronal cell death, through the formation of Ca-permeable membrane pores, impairment in the levels of acetylcholine neurotransmitters, increased insulin resistance, promotion of pro-inflammatory cascades, among others. Based on a series of evidences that indicate the key role of glycosaminoglycans (GAGs) in amyloid plaque formation, we evaluated the capacity of four monosaccharides, i.e., glucosamine (GlcN), -acetyl glucosamine (GlcNAc), glucosamine-6-sulfate (GlcN6S), and glucosamine-6-phosphate (GlcN6P), to reduce the Aβ-mediated pathological hallmarks. The tested monosaccharides, in particular, GlcN6S and GlcN6P, were able to interact with Aβ aggregates, reducing neuronal cell death, Aβ-mediated damage to the cellular membrane, acetylcholinesterase activity, insulin resistance, and pro-inflammation levels.
在阿尔茨海默病（AD）中，淀粉样β蛋白（Aβ）寡聚体被认为是突触功能障碍和认知障碍的关键介质。这些不稳定的中间Aβ物种可通过形成钙离子通透膜孔、损害乙酰胆碱神经递质水平、增加胰岛素抵抗、促进促炎级联反应等方式干扰不同的细胞器，导致神经元细胞死亡。基于一系列表明糖胺聚糖（GAGs）在淀粉样斑块形成中起关键作用的证据，我们评估了四种单糖，即氨基葡萄糖（GlcN）、N-乙酰氨基葡萄糖（GlcNAc）、6-硫酸氨基葡萄糖（GlcN6S）和6-磷酸氨基葡萄糖（GlcN6P）减少Aβ介导的病理特征的能力。所测试的单糖，特别是GlcN6S和GlcN6P，能够与Aβ聚集体相互作用，减少神经元细胞死亡、Aβ介导的细胞膜损伤、乙酰胆碱酯酶活性、胰岛素抵抗和促炎水平。
