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

1 Citation (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
Journal	ACS Applied Materials and Interfaces
DOIs	https://doi.org/10.1021/acsami.2c14650
Publication status	Accepted/In press - 2022

Bibliographical note

Funding Information:
This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean Government (MSIP) (nos. NRF-2018M3C1B7020722, NRF-2020R1A2C2102262, NRF-2022R1A6A3A13072828, NRF-2022R1A2C1091756 and NRF-2022R1A6A3A03066467), BK21 Four Institute of Precision Public Health, and the Korea University Graduate School Junior Fellow Research Grant. This work was also supported by the Bio & Medical Technology Development Program of the NRF funded by the Korean government (MSIT) (no. 2021M3E5E3080743) and Korea Health Industry Development Institute (KHIDI) grant HU21C0053.

Publisher Copyright:
©

Keywords

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

ASJC Scopus subject areas

Materials Science(all)

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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. (Accepted/In press). Biomimetically Engineered Amyloid-Shelled Gold Nanocomplexes for Discovering α-Synuclein Oligomer-Degrading Drugs. ACS Applied Materials and Interfaces. https://doi.org/10.1021/acsami.2c14650

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title = "Biomimetically Engineered Amyloid-Shelled Gold Nanocomplexes for Discovering α-Synuclein Oligomer-Degrading Drugs",

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.",

keywords = "Parkinson's disease, amyloid corona, drug screening, plasmonic nanoparticle, α-synuclein",

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

note = "Funding Information: This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean Government (MSIP) (nos. NRF-2018M3C1B7020722, NRF-2020R1A2C2102262, NRF-2022R1A6A3A13072828, NRF-2022R1A2C1091756 and NRF-2022R1A6A3A03066467), BK21 Four Institute of Precision Public Health, and the Korea University Graduate School Junior Fellow Research Grant. This work was also supported by the Bio & Medical Technology Development Program of the NRF funded by the Korean government (MSIT) (no. 2021M3E5E3080743) and Korea Health Industry Development Institute (KHIDI) grant HU21C0053. Publisher Copyright: {\textcopyright} ",

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doi = "10.1021/acsami.2c14650",

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journal = "ACS Applied Materials and Interfaces",

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AU - Lee, Dongtak

AU - Jung, Hyo Gi

AU - Park, Dongsung

AU - Bang, Junho

AU - Hong, Ji Hye

AU - Lee, Sang Won

AU - Roh, Seokbeom

AU - Jang, Jae Won

AU - Kim, Yonghwan

AU - Hwang, Kyo Seon

AU - Lee, Young Sun

AU - Park, Jae Yong

AU - Jung, In Duk

AU - Lee, Jeong Hoon

AU - Lee, Gyudo

AU - Yoon, Dae Sung

N1 - Funding Information: This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean Government (MSIP) (nos. NRF-2018M3C1B7020722, NRF-2020R1A2C2102262, NRF-2022R1A6A3A13072828, NRF-2022R1A2C1091756 and NRF-2022R1A6A3A03066467), BK21 Four Institute of Precision Public Health, and the Korea University Graduate School Junior Fellow Research Grant. This work was also supported by the Bio & Medical Technology Development Program of the NRF funded by the Korean government (MSIT) (no. 2021M3E5E3080743) and Korea Health Industry Development Institute (KHIDI) grant HU21C0053. Publisher Copyright: ©

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - Parkinson's disease

KW - amyloid corona

KW - drug screening

KW - plasmonic nanoparticle

KW - α-synuclein

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DO - 10.1021/acsami.2c14650

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SN - 1944-8244

JO - ACS Applied Materials and Interfaces

JF - ACS Applied Materials and Interfaces

ER -

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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