Biomimetically Engineered Amyloid-Shelled Gold Nanocomplexes for Discovering α‑Synuclein Oligomer-Degrading Drugs

Dongtak Lee; Hyo Gi Jung; Dongsung Park; Junho Bang; Ji Hye Hong; Sang Won Lee; Seokbeom Roh; Jae Won Jang; Yonghwan Kim; Kyo Seon Hwang; Young Sun Lee; Jae Yong Park; In Duk Jung; Jeong Hoon Lee; Gyudo Lee; Dae Sung Yoon

doi:10.1021/acsami.2c14650

Biomimetically Engineered Amyloid-Shelled Gold Nanocomplexes for Discovering α‑Synuclein Oligomer-Degrading Drugs

Dongtak Lee, Hyo Gi Jung, Dongsung Park, Junho Bang, Ji Hye Hong, Sang Won Lee, Seokbeom Roh, Jae Won Jang, Yonghwan Kim, Kyo Seon Hwang, Young Sun Lee, Jae Yong Park, In Duk Jung, Jeong Hoon Lee, Gyudo Lee, Dae Sung Yoon

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

Abstract

The assembly of α-synuclein (αS) oligomers is recognized as the main pathological driver of synucleinopathies. While the elimination of toxic αS oligomers shows promise for the treatment of Parkinson’s disease (PD), the discovery of αS oligomer degradation drugs has been hindered by the lack of proper drug screening tools. Here, we report a drug screening platform for monitoring the efficacy of αS-oligomer-degrading drugs using amyloid-shelled gold nanocomplexes (ASGNs). We fabricate ASGNs in the presence of dopamine, mimicking the in vivo generation process of pathological αS oligomers. To test our platform, the first of its kind for PD drugs, we use αS-degrading proteases and various small molecular substances that have shown efficacy in PD treatment. We demonstrate that the ASGN-based in vitro platform has strong potential to discover effective αS-oligomer-targeting drugs, and thus it may reduce the attrition problem in drug discovery for PD treatment.

Original language	English
Pages (from-to)	2538-2551
Number of pages	14
Journal	ACS Applied Materials and Interfaces
Volume	15
Issue number	2
DOIs	https://doi.org/10.1021/acsami.2c14650
Publication status	Published - 2023

Bibliographical note

Publisher Copyright:
© 2022 American Chemical Society.

Keywords

Parkinson’s disease
amyloid corona
drug screening
plasmonic nanoparticle
α-synuclein

ASJC Scopus subject areas

General Materials Science

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10.1021/acsami.2c14650

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Lee, D., Jung, H. G., Park, D., Bang, J., Hong, J. H., Lee, S. W., Roh, S., Jang, J. W., Kim, Y., Hwang, K. S., Lee, Y. S., Park, J. Y., Jung, I. D., Lee, J. H., Lee, G., & Yoon, D. S. (2023). Biomimetically Engineered Amyloid-Shelled Gold Nanocomplexes for Discovering α‑Synuclein Oligomer-Degrading Drugs. ACS Applied Materials and Interfaces, 15(2), 2538-2551. https://doi.org/10.1021/acsami.2c14650

Lee, D, Jung, HG, Park, D, Bang, J, Hong, JH, Lee, SW, Roh, S, Jang, JW, Kim, Y, Hwang, KS, Lee, YS, Park, JY, Jung, ID, Lee, JH, Lee, G & Yoon, DS 2023, 'Biomimetically Engineered Amyloid-Shelled Gold Nanocomplexes for Discovering α‑Synuclein Oligomer-Degrading Drugs', ACS Applied Materials and Interfaces, vol. 15, no. 2, pp. 2538-2551. https://doi.org/10.1021/acsami.2c14650

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abstract = "The assembly of α-synuclein (αS) oligomers is recognized as the main pathological driver of synucleinopathies. While the elimination of toxic αS oligomers shows promise for the treatment of Parkinson{\textquoteright}s disease (PD), the discovery of αS oligomer degradation drugs has been hindered by the lack of proper drug screening tools. Here, we report a drug screening platform for monitoring the efficacy of αS-oligomer-degrading drugs using amyloid-shelled gold nanocomplexes (ASGNs). We fabricate ASGNs in the presence of dopamine, mimicking the in vivo generation process of pathological αS oligomers. To test our platform, the first of its kind for PD drugs, we use αS-degrading proteases and various small molecular substances that have shown efficacy in PD treatment. We demonstrate that the ASGN-based in vitro platform has strong potential to discover effective αS-oligomer-targeting drugs, and thus it may reduce the attrition problem in drug discovery for PD treatment.",

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Biomimetically Engineered Amyloid-Shelled Gold Nanocomplexes for Discovering α‑Synuclein Oligomer-Degrading Drugs

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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