Dissolution of amyloid aggregates by direct addition of alkali halides

Abstract

The development of standard dissolution agents for various amyloid aggregates in vitro is essential to acquire basic information on pharmaceutical treatment strategies and improve the recovery rate for target expressed proteins. Nevertheless, no standard dissolution agents are currently applied to many amyloid aggregates. Thus, to proceed one step further, the dissolution ability of α-synuclein amyloid aggregates (α-synuclein amyloid) formed under mild conditions (pD 7.5 and 310 K) was investigated using the direct addition of alkali halides. Fourier-transform infrared spectroscopy and Congo red assay were used to evaluate the efficacy of the dissolution agents of alkali halides for amyloid aggregates. The effects of alkali halides on α- synuclein amyloid were classified into three types: (i) dissolution effect, (ii) no effect, and (iii) promotion effect. These effects correlate with the disruption ability of cations (the direct effect) and the solvation free energy difference (ΔΔGSolv) between the cations and anions (the indirect effect). Remarkably, lithium iodide (LiI) has the strongest dissolution ability for α-synuclein amyloid among the examined alkali halides. Furthermore, dialysis can recover the monomer state from α-synuclein amyloid dissolved in LiI. In addition, LiI also exhibits a strong dissolution ability for bovine insulin amyloid aggregates formed under extreme conditions (pD 1.6 and 363 K). These findings show that LiI has the potential as a standard dissolution agent applied to amyloid aggregates among the alkali halides.