Litus Ekaterina A, Shevelyova Marina P, Vologzhannikova Alisa A, Deryusheva Evgenia I, Machulin Andrey V, Nemashkalova Ekaterina L, Permyakova Maria E, Sokolov Andrey S, Alikova Valeria D, Uversky Vladimir N, Permyakov Sergei E
Institute for Biological Instrumentation, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, Institutskaya Str., 7, Pushchino, 142290 Moscow, Russia.
Skryabin Institute of Biochemistry and Physiology of Microorganisms, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, pr. Nauki, 5, Pushchino, 142290 Moscow, Russia.
Biomolecules. 2025 Mar 17;15(3):431. doi: 10.3390/biom15030431.
Human serum albumin (HSA) is a natural depot of amyloid-β peptide (Aβ), a key player in Alzheimer's disease (AD). HSA and pro-inflammatory Ca-binding proteins S100A8 and S100A9 are involved in Aβ metabolism and its deposition in the brain, serving as probable triggers and therapeutic targets in AD, but their interplay with regard to Aβ binding/fibrillation is unclear. To this end, here we explore the in vitro binding of Ca-bound S100A8 or S100A9 to monomeric Aβ and the influence of the S100 proteins on Aβ fibrillation. The equilibrium dissociation constants of the complexes of dimeric S100A8/S100A9 with Aβ40/42 estimated by biolayer interferometry are 1-5 µM. S100A8 and S100A9 interfere with HSA binding to Aβ. Thioflavin T assay and electron microscopy data show that micromolar S100A8/S100A9 inhibit Aβ40 fibrillation, and the inhibitory effect of S100A8 exceeds that for HSA. The competition for Aβ between HSA and S100A8/S100A9 may contribute to the Aβ-HSA imbalance in the pro-inflammatory conditions in AD.
人血清白蛋白（HSA）是淀粉样β肽（Aβ）的天然储存库，Aβ是阿尔茨海默病（AD）的关键因素。HSA和促炎钙结合蛋白S100A8及S100A9参与Aβ代谢及其在大脑中的沉积，可能是AD的触发因素和治疗靶点，但其在Aβ结合/纤维化方面的相互作用尚不清楚。为此，我们在此探究钙结合的S100A8或S100A9与单体Aβ的体外结合以及S100蛋白对Aβ纤维化的影响。通过生物层干涉术估算的二聚体S100A8/S100A9与Aβ40/42复合物的平衡解离常数为1 - 5 μM。S100A8和S100A9会干扰HSA与Aβ的结合。硫黄素T检测和电子显微镜数据表明，微摩尔浓度的S100A8/S100A9可抑制Aβ40纤维化，且S100A8的抑制作用超过HSA。HSA与S100A8/S100A9之间对Aβ的竞争可能导致AD促炎状态下Aβ - HSA失衡。
