Original ArticleRapid and high-throughput colorimetric screening for anti-aggregation reagents of protein conformational diseases by using gold nanoplasmonic particles
Graphical Abstract
Gold nanoparticles can accelerate protein aggregation as nucleation cores and facilitate monitoring the aggregation process as optical reporters. Here, we demonstrated rapid, high-throughput colorimetric screening method for discovering anti-aggregation reagents from numerous chemicals for protein conformational diseases. Using the gold nanoparticles, we observed colorimetric responses to anti-aggregation effect for amyloid β (implicated in Alzheimer's disease) with the naked eye within a few minutes and quantified the anti-aggregation efficiency by measuring absorbance changes. Furthermore, results obtained with spiked samples in cerebrospinal fluid as well as under various denaturation conditions and different amyloid β compositions show the feasibility of future personalized medicine.
Section snippets
Materials
Amyloid β fragment 1–40 [Aβ (1–40)] and amyloid β fragment 1–42 [Aβ (1–42)] were purchased from AnaSpec, Inc. (Fremont, CA, USA). Albumin, (−)-epigallocatechin gallate, resveratrol, acetylcholine chloride, rutin hydrate, silibinin, and curcumin from Curcuma longa were purchased from Sigma-Aldrich Co. LLC (St. Louis, MO, USA). Caffeine, trehalose dihydrate, and glutathione (reduced form) were purchased from Wako (Chou-ku, Osaka, Japan). All water used in our experiment was purified to 18.3 MΩ.
Preparation of GNPs
Nanoparticle-assisted rapid protein aggregation and its colorimetric monitoring
To confirm that GNPs can accelerate the aggregation process, we tested two types of representative amyloid β (Aβ) peptides, Aβ (1–40) and Aβ (1–42), found abundantly in patients with Alzheimer's disease. Denaturation of these peptides by various aggregation-promoting conditions induces the deposition of Aβ aggregates in brain tissue.32 For example, physiologically relevant low pH level has been widely accepted as a representative destabilizing condition causing Aβ aggregates.26, 33, 34 For this
Discussion
In our study, we utilized GNPs to develop a fast, simple and easy method for screening anti-aggregation reagents out of a number of possible drug candidates for Alzheimer's disease where Aβ aggregation is closely involved. Main benefits of using GNPs are that they are less toxic than other inorganic nanoparticles (e.g., silver nanoparticles and quantum dots) and that their sizes and surface properties can be easily tuned. Owing to these properties of the GNPs, they have been extensively
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Financial support information:
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT & Future Planning (2014R1A1A1038069). This research was also supported by the Mid-Career Researcher Support Program (No. 2016R1A2B3014157), and by Basic Science Research Program (No. 2016R1A6A1A03012845) through the National Research Foundation of Korea funded by the Ministry of Science, ICT, and Future Planning.
The authors declare no competing financial interest.