Inhibition of Protein Aggregation by Several Antioxidants

Abstract

Amyloid fibril formation is a shared property of all proteins; therefore, model proteins can be used to study this process. We measured protein aggregation of the model amyloid-forming protein stefin B in the presence and absence of several antioxidants. Amyloid fibril formation by stefin B was routinely induced at pH 5 and 10% TFE, at room temperature. The effects of antioxidants NAC, vitamin C, vitamin E, and the three polyphenols resveratrol, quercetin, and curcumin on the kinetics of fibril formation were followed using ThT fluorescence. Concomitantly, the morphology and amount of the aggregates and fibrils were checked by transmission electron microscopy (TEM). The concentration of the antioxidants was varied, and it was observed that different modes of action apply at low or high concentrations relative to the binding constant. In order to obtain more insight into the possible mode of binding, docking of NAC, vitamin C, and all three polyphenols was done to the monomeric form of stefin B.

Modulating disease-relevant tau oligomeric strains by small molecules

“…Therefore, early diagnosis of these disorders, prior to the progression of the pathology, may enhance the chances of success of potential therapeutic approaches ( 28 – 31 ). Over the past 10 years, many approaches targeting tau aggregates, including small molecules, have been an area of great interest for drug discovery to develop effective disease-modifying therapeutics ( 11 , 32 – 35 ).…”

Antioxidants From the Class of Polyphenols, NAC and Vitamin C Act Differently on Amyloid Fibril Formation by Two Human Cystatins: Stefin B and Cystatin C.

“…As studied by Hasanbasić et al 31 Regardless of the similarly structured amyloid core with the cross-β structure, this may be explained by an assumption that sequence details and precise arrangement of the subunits in the protofilaments influence aromatic-aromatic π stacking interactions 34 . Indeed, precise arrangement of protofilaments can influence π stacking 35,36 and the same protein can form polymorphic amyloid fibrils, which have specific chemical and biological properties 37,38 .…”

“…New experiments (synergistic effect of vitC and polyphenols) were studied by the same methods as described before. The details have been described in papers by Jahic et al 33 for cysC and Hasanbasic, Jahic et al 31 for stB.…”

An Overview of Crucial Dietary Substances and Their Modes of Action for Prevention of Neurodegenerative Diseases

“…In parallel, it was shown that polyphenols from tea lowered the levels of oligomers while enhancing the cell viability in a DAergic substantia nigra/neuroblastoma hybrid cell line known as MES23.5 cells, when they were treated with the combination of MPP+ and α-synuclein monomers or oligomers. Other polyphenols have also shown fibril-destabilizing properties through inhibition of initiation and/or propagation of α-synuclein fibrils in vitro, including quercetin [146,147], curcumin [147][148][149], and its metabolites [150], chlorogenic acid [151], and resveratrol [147]. Interestingly, the oxidized form of quercetin was more efficient at destabilization of human wild-type α-synuclein formation of fibrils and their growth [146].…”