Abstract
Natural products have played a dominant role in the discovery of lead compounds for the development of drugs aimed at the treatment of human diseases. This electrospray ionization-ion mobility spectrometry-mass spectrometry (ESI-IMS-MS)—based study demonstrates that dietary antioxidants, isolated components from the stigmas of saffron (Crocus sativus L.) may be effective in inhibiting Aβ fibrillogenesis, a neuropathological hallmark of Alzheimer’s Disease (AD). This study reveals a substantial alteration in the monomer/oligomer distribution of Aβ1-40, concomitant with re-direction of fibril formation, induced by the natural product interaction. These alterations on the Aβ1-40 aggregation pathway are most prominent for trans-crocin-4 (TC4). Use of ESI-IMS-MS, electron microscopy alongside Thioflavin-T kinetics, and the interpretation of 3-dimensional Driftscope plots indicate a correlation of these monomer/oligomer distribution changes with alterations to Aβ1-40 amyloid formation. The latter could prove instrumental in the development of novel aggregation inhibitors for the prevention, or treatment of AD.
Highlights
Natural products have played a dominant role in the discovery of lead compounds for the development of drugs aimed at the treatment of human diseases
Weak signals corresponding to multiply charged ions of the dimer (+5 to +7) were observed in the ESI mass spectrum. These ions were more pronounced in the analysis of Aβ1-40 by ESI-IMS-MS, where signals corresponding to Aβ1-40 oligomers ranging from dimer to heptamers were readily detected in the ESIIMS-MS driftscope plot of the Aβ1-40 monomer (Fig. 2c), demonstrating formation of Aβ1-40 aggregated species
This study demonstrates that dietary antioxidants and especially isolated components from the stigmas of saffron (Crocus sativus L.) may be effective in re-directing the pathway of Aβ aggregation
Summary
Natural products have played a dominant role in the discovery of lead compounds for the development of drugs aimed at the treatment of human diseases This electrospray ionization-ion mobility spectrometry-mass spectrometry (ESI-IMS-MS)—based study demonstrates that dietary antioxidants, isolated components from the stigmas of saffron (Crocus sativus L.) may be effective in inhibiting Aβ fibrillogenesis, a neuropathological hallmark of Alzheimer’s Disease (AD). Inhibiting formation of Aβ oligomeric states and amyloid fibril by small molecule binding to the peptide has been proposed as a viable therapeutic strategy[10] Both the Aβ1-40 and Aβ1-42 variants have been shown to exist as monomeric forms in rapid equilibrium with the corresponding soluble oligomers, and they self-assemble via different and distinct pathways as previously reported[11,12]. The latter may be significant for identifying targets and designing putative inhibitors, and it could be invaluable towards shedding some light into the pathways of oligomer formation in amyloid disease
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
