Araujo_2021_ACS.Med.Chem.Lett_12_548

In Alzheimer's disease (AD), amyloid-beta (Abeta) oligomers are considered key mediators of synaptic dysfunction and cognitive impairment. These unstable intermediate Abeta species can interfere with different cellular organelles, leading to neuronal cell death, through the formation of Ca(2+)-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), N-acetyl glucosamine (GlcNAc), glucosamine-6-sulfate (GlcN6S), and glucosamine-6-phosphate (GlcN6P), to reduce the Abeta-mediated pathological hallmarks. The tested monosaccharides, in particular, GlcN6S and GlcN6P, were able to interact with Abeta aggregates, reducing neuronal cell death, Abeta-mediated damage to the cellular membrane, acetylcholinesterase activity, insulin resistance, and pro-inflammation levels.