Alzheimer’s Disease, Human Serum Albumin, Amyloid β Peptide, Serotonin, Tryptophan, Surface Plasmon Resonance, Molecular Docking, Intrinsic Disorder
Digital Object Identifier (DOI)
Prevention of amyloid β peptide (Aβ) deposition via facilitation of Aβ binding to its natural depot, human serum albumin (HSA), is a promising approach to preclude Alzheimer’s disease (AD) onset and progression. Previously, we demonstrated the ability of natural HSA ligands, fatty acids, to improve the affinity of this protein to monomeric Aβ by a factor of 3 (BBRC, 510(2), 248–253). Using plasmon resonance spectroscopy, we show here that another HSA ligand related to AD pathogenesis, serotonin (SRO), increases the affinity of the Aβ monomer to HSA by a factor of 7/17 for Aβ40/Aβ42, respectively. Meanwhile, the structurally homologous SRO precursor, tryptophan (TRP), does not affect HSA’s affinity to monomeric Aβ, despite slowdown of the association and dissociation processes. Crosslinking with glutaraldehyde and dynamic light scattering experiments reveal that, compared with the TRP-induced effects, SRO binding causes more marked changes in the quaternary structure of HSA. Furthermore, molecular docking reveals distinct structural differences between SRO/TRP complexes with HSA. The disintegration of the serotonergic system during AD pathogenesis may contribute to Aβ release from HSA in the central nervous system due to impairment of the SRO-mediated Aβ trapping by HSA.
This work is licensed under a Creative Commons Attribution 4.0 License.
Was this content written or created while at USF?
Citation / Publisher Attribution
International Journal of Molecular Sciences, v. 22, issue 11, art. 5896
Scholar Commons Citation
Litus, Ekaterina A.; Kazakov, Alexei S.; Deryusheva, Eugenia I.; Nemashkalova, Ekaterina L.; Shevelyova, Marina P.; Nazipova, Aliya A.; Permyakova, Maria E.; Raznikova, Elena V.; Uversky, Vladimir N.; and Permyakov, Sergei E., "Serotonin Promotes Serum Albumin Interaction with the Monomeric Amyloid β Peptide" (2021). Molecular Medicine Faculty Publications. 892.