Crocus-derived compounds alter the aggregation pathway of Alzheimer’s Disease: associated beta amyloid protein

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.

Early stages of insulin fibrillogenesis examined with ion mobility mass spectrometry and molecular modelling

Mass spectrometry shows insulin oligomers [I]nwhere n ranges from 1-12, and ion mobility analysis reveals ∼60 structurally distinct species across this oligomer distribution. Experimental data trains MD simulations to characterize a persistent prefibrillar protein oligomer that is a dimer enriched in β sheets.