Institute for Biological Instrumentation, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, 142290 Pushchino, Russia.
Skryabin Institute of Biochemistry and Physiology of Microorganisms, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, 142290 Pushchino, Russia.
Int J Mol Sci. 2022 May 31;23(11):6168. doi: 10.3390/ijms23116168.
The deposition of amyloid-β peptide (Aβ) in the brain is a critical event in the progression of Alzheimer's disease (AD). This Aβ deposition could be prevented by directed enhancement of Aβ binding to its natural depot, human serum albumin (HSA). Previously, we revealed that specific endogenous ligands of HSA improve its affinity to monomeric Aβ. We show here that an exogenous HSA ligand, ibuprofen (IBU), exerts the analogous effect. Plasmon resonance spectroscopy data evidence that a therapeutic IBU level increases HSA affinity to monomeric Aβ/Aβ by a factor of 3-5. Using thioflavin T fluorescence assay and transmission electron microcopy, we show that IBU favors the suppression of Aβ fibrillation by HSA. Molecular docking data indicate partial overlap between the IBU/Aβ-binding sites of HSA. The revealed enhancement of the HSA-Aβ interaction by IBU and the strengthened inhibition of Aβ fibrillation by HSA in the presence of IBU could contribute to the neuroprotective effects of the latter, previously observed in mouse and human studies of AD.
淀粉样蛋白-β肽（Aβ）在大脑中的沉积是阿尔茨海默病（AD）进展的关键事件。通过定向增强 Aβ与其天然储库人血清白蛋白（HSA）的结合，可以预防这种 Aβ沉积。先前，我们揭示了 HSA 的特定内源性配体可以提高其与单体 Aβ的亲和力。我们在这里表明，外源性 HSA 配体布洛芬（IBU）具有类似的作用。等离子体共振光谱数据表明，治疗性 IBU 水平使 HSA 对单体 Aβ/Aβ的亲和力提高了 3-5 倍。使用硫黄素 T 荧光测定法和透射电子显微镜，我们表明 IBU 有利于 HSA 抑制 Aβ纤丝形成。分子对接数据表明，IBU 与 HSA 的 Aβ 结合位点存在部分重叠。IBU 增强 HSA-Aβ 相互作用以及 IBU 存在时 HSA 对 Aβ 纤丝形成的抑制作用增强，可能有助于后者在 AD 的小鼠和人体研究中观察到的神经保护作用。
