Study of the interaction between the amyloid beta peptide (1-40) and antioxidant compounds by nuclear magnetic resonance spectroscopy

Abstract

Amyloid beta peptide (Abeta) aggregation leads to the senile plaque formation, a process that is strongly influenced by oxidative stress and is considered as the molecular basis of various neurodegenerative diseases, such as Alzheimer's disease (AD). Endogenous antioxidants or dietary derived compounds may down-regulate this process. In this study, the interaction of two antioxidants, oleuropein (OE) and melatonin (M), with Abeta is monitored through nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry. The concerted application of these two analytical techniques provides new experimental evidence and residue-specific insights into the interacting Abeta peptide amino acids that are implicated in this process. Both antioxidant compounds interact in a similar way with the peptide and cause chemical shift variations. The most pronounced resonance changes have been observed for the 1H-15N signals of N-terminal region and Leu17-Phe20 residues, as monitored by NMR titration studies.

Protein aggregation and neurodegeneration in prototypical neurodegenerative diseases: Examples of amyloidopathies, tauopathies and synucleinopathies

“…These compounds, along with several novel hydroxytyrosol derivatives possessing structural analogy to oleuropein (OE), were screened for binding with Ab peptide employing electrospray ionization (ESI) MS (Ganguly et al, 2002;Loo, 2000). The formation of 1:1 noncovalent complexes of Ab with certain antioxidants such as oleuropein (OE) and melatonin (M) has been previously demonstrated by ESI MS (Bazoti et al, 2005(Bazoti et al, , 2006, while their interaction with the hydrophobic region of the peptide has been reported by ESI MS proteolytic mapping studies (Bazoti et al, 2008) and NMR (Galanakis et al, 2011). Similar 1:1 noncovalent interactions between the Ab peptide and the main crocin components TC-2, TC-3 and TC-4, were also observed in this study (Koulakiotis et al, 2014).…”

Small Amphipathic Molecules Modulate Secondary Structure and Amyloid Fibril-forming Kinetics of Alzheimer Disease Peptide Aβ1–42

“…On the basis of previous work on various other small molecule modulators of A␤ aggregation, such as 8-hydroxyquinolines (42), oleuropein (43,44), ␣-helix stabilizers (45), various chaperones (46,47), anesthetics (48,49), and gangliosides (50), two potential binding sites can be suggested. From these previous studies it is clear that A␤ contains a small molecule binding site near residues 10 -20 and a second binding site in the C-terminal glycine zipper motif.…”

Targeting Assembly and Disassembly of Protein Aggregates

“…Disordered Ab-oleuropein aggregates resulting from pre-incubation with oleuropein aglycone, conversely, are not neurotoxic to neurons [198]. The binding between Ab peptides and oleuropein is structurally characterized by NMR (hydrophobic interactions with Leu17-Phe20 region, hydrophilic interactions with N-terminus and His13-Lys16 regions) [199]. Three-month-old double Sweden-Indiana/V717F TG mice treated with oleuropein aglycone (50 mg/kg daily with food, 8 weeks) show memory improvements and a lower Ab burden [200].…”