Study of Morin inhibitory effect on the insulin fibrillogenesis

Protein misfolding and aggregation are associated with a growing number of neurodegenerative disorders, including Alzheimer s, Parkinson s, and Huntington s diseases, and type II diabetes. A common feature among these diseases is the misfolding and subsequent aggregation of different proteins and peptides into polymeric forms that are characterized by cross-β structures and referred to as amyloid fibrils. Among strategies developed to inhibit protein aggregation and amyloid fibril formation most therapeutic approaches are mainly based on prevention of amyloid fibril formation or promoting clearance of amyloid aggregates. Therefore, considerable efforts are being devoted to the development of new anti-aggregating agents, particularly in relation to amyloid-related peptides and proteins, under both in vitro and in vivo conditions. In this regard, there are many reports suggesting natural polyphenols as effective inhibitors of amyloid fibril formation. In the present study, using a range of techniques including ThT and ANS fluorescence measurements, and Congo red binding assay the effect of Morin, as a natural occurring polyphenol, on the inhibition of insulin amyloid fibril formation has been investigated .The obtained results revealed that Morin effectively reduces amount of amyloid fibrils in a concentration dependent manner. While, atomic force microscopy revealed the formation of typical amyloid fibrils in control samples, the presence of Morin significantly inhibits the formation of amyloid aggregates. However, additional studies are needed to elucidate the detailed mechanisms by which Morin exert its inhibitory effects. We believe that results presented may provide useful guidelines in relation to screening for novel inhibitors against protein misfolding and aggregation associated with neurodegenerative diseases.