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

被引：2

作者：

Lee, Dongtak ^{[1
]}

Jung, Hyo Gi ^{[1
,2
]}

Park, Dongsung ^{[1
,3
]}

Bang, Junho ^{[1
,2
]}

Hong, Ji Hye ^{[1
]}

Lee, Sang Won ^{[1
]}

Roh, Seokbeom ^{[4
,5
]}

Jang, Jae Won ^{[1
,2
]}

Kim, Yonghwan ^{[1
,2
]}

Hwang, Kyo Seon ^{[3
]}

Lee, Young-Sun ^{[6
,7
]}

Park, Jae-Yong ^{[6
,7
]}

Jung, In Duk ^{[6
]}

Lee, Jeong Hoon ^{[8
]}

Lee, Gyudo ^{[4
,5
]}

Yoon, Dae Sung ^{[1
,2
]}

机构：

[1] Korea Univ, Sch Biomed Engn, Seoul 02841, South Korea

[2] Korea Univ, Interdisciplinary Program Precis Publ Hlth, Seoul 02841, South Korea

[3] Kyung Hee Univ, Coll Med, Dept Clin Pharmacol & Therapeut, Seoul 02447, South Korea

[4] Dept Biotechnol & Bioinformat, Sejong 30019, South Korea

[5] Interdisciplinary Grad Program Artificial Intellig, Sejong 30019, South Korea

[6] ASTRION, Seoul 02842, South Korea

[7] Korea Univ, Coll Hlth Sci, Sch Biosyst & Biomed Sci, Seoul 02841, South Korea

[8] Kwangwoon Univ, Dept Elect Engn, Seoul 01897, South Korea

来源：

ACS APPLIED MATERIALS & INTERFACES | 2023年 / 15卷 / 02期

基金：

新加坡国家研究基金会;

关键词：

-synuclein; Parkinson?s disease; plasmonic nanoparticle; drug screening; amyloid corona; DISORDER;

D O I：

10.1021/acsami.2c14650

中图分类号：

TB3 [工程材料学];

学科分类号：

0805 ; 080502 ;

摘要：

The assembly of alpha-synuclein (alpha S) oligomers is recognized as the main pathological driver of synucleinopathies. While the elimination of toxic alpha S oligomers shows promise for the treatment of Parkinson's disease (PD), the discovery of alpha S 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 alpha S-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 alpha S oligomers. To test our platform, the first of its kind for PD drugs, we use alpha S-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 alpha S-oligomer-targeting drugs, and thus it may reduce the attrition problem in drug discovery for PD treatment.

引用

页码：2538 / 2551

页数：14

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