Triiodide ion-induced inhibition of amyloid aggregate formation: A case study of α-synuclein

Abstract

• The effect of ethylammonium iodide (EAI) on the formation of amyloid aggregates of α-synuclein (α-SynA) was investigated. • Concentrated EAI solutions exhibited an ability to inhibit α-SynA formation. • The formation of triodide (I 3 – ) ion in this media relates to the inhibition of α-SynA formation. • The inhibition ability of ammonium-based iodides for α-SynA formation are stronger than alkali-iodides. Small compounds that inhibit amyloid protein formation are of interest for the development of anti-amyloidogenic agents. We focused on iodide salts, which are widely used in tablets, supplements, disinfectants, and pharmaceuticals, as anti-amyloidogenic agents in vitro . We performed optical spectroscopy to investigate the effects of ethylammonium iodide (EAI) as an anti-amyloidogenic agent on the formation of amyloid aggregates (neutral pD and 310 K) of human α-synuclein (α-Syn) over a wide range of EAI concentrations. Fourier-transform infrared spectral analysis and a congo red assay revealed that concentrated EAI solutions could inhibit the formation of α-Syn amyloid aggregates (α-SynA). UV–Vis and Raman spectra showed that triiodide (I 3 − ) ion formation occurred in aqueous EAI solution, and clarified that the I 3 – ion relates to the inhibition of α-SynA formation because of the interactions with the peptide backbone and positively charged region in the N-terminal region of α-Syn. In addition to EAI, ammonium iodide (NH 4 I) and methylammonium iodide (MAI) also inhibited α-SynA: NH 4 I and MAI form the I 3 − ion. The inhibition ability of these two salts are stronger than alkali-iodides (KI and NaI). The present results suggest that ammonium iodides that form I 3 − ions have the potential to be effective anti-amyloidogenic agents for α-Syn.