Ibuprofen Favors Binding of Amyloid-β Peptide to Its Depot, Serum Albumin

Abstract

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 Aβ40/Aβ42 by a factor of 3–5. Using thioflavin T fluorescence assay and transmission electron microcopy, we show that IBU favors the suppression of Aβ40 fibrillation by HSA. Molecular docking data indicate partial overlap between the IBU/Aβ40-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.

Virtual Screening of Human Serum Albumin Mutants to Optimize the Search for its Forms that Increase Affinity to Amyloid-Β Peptide

“…The results obtained are consistent with the data of epidemiological and animal AD studies [17,18]. Ibuprofen enhances the affinity of HSA to monomeric Aβ and intensifies inhibitory the effect of HSA toward Aβ fibrillation, that in line with data on a reduction in the risk of AD development long-term ibuprofen intake [26].…”

“…2A) correspond to surface and/or disordered regions that play a key role in HSA interactions with low weight, peptide and protein ligands [33]. In addition, some of these regions are located in regions between I and III domains, as well as between II and III structural domains, which corresponds to the localization of probable binding sites with monomeric and oligomeric forms of Aβ, according to the results of experimental and molecular dynamics studies [25], as well as bioinformatics studies [26].…”

Effect of Laser-Induced Optical Breakdown on the Structure of Bsa Molecules in Aqueous Solutions: An Optical Study

“…The generation of ultraviolet radiation, shock acoustic waves, and microvolumes with a significant increase in temperature is observed [ 35 ]. With such a set of influences, the following can be observed: (1) chemical modification of amino acid residues; (2) fragmentation of the polypeptide chain; (3) change in the tertiary and secondary structure of BSA molecules; (4) partial denaturation; and (5) aggregation of molecules [ 36 , 37 , 38 , 39 ]. It should be noted that a similar set of events occurs with proteins under the action of oxidative stress [ 40 ], which develops in living systems under the action of various physical and chemical factors [ 41 ], during the development of inflammation [ 42 ], hypoxia [ 43 ], and a number of diseases [ 44 ], etc.…”

In Search for the Low-Molecular-Weight Ligands of Human Serum Albumin that Affect its Affinity for Monomeric Amyloid β Peptide

“…The potentially less harmful approach is to increase HSA affinity for Aβ via allosteric action of endogenous or exogenous HSA ligands, initially demonstrated for linoleic and arachidonic acids [30]. We further showed the even more pronounced effects for serotonin [31] and ibuprofen [32]. Moreover, ibuprofen enhances HSA ability to inhibit Aβ fibrillation [32].…”