DataVXACS Applied Materials & InterfacesPaper
journal article·2021-12-29

Polyglutamine-Specific Gold Nanoparticle Complex Alleviates Mutant Huntingtin-Induced Toxicity

Devi Wahyuningtyas, Wen-Hao Chen, Ruei-Yu He, Yung-An Huang, Chia-Kang Tsao, Yu-Jung He, Chu-Yi Yu, Po-Chao Lu, Yu-Cai Chen, Sheng-Hann Wang, Ka Chon Ng, Bryan Po-Wen Chen, Pei-Kuen Wei, Jiun-Jie Shie, Chun-Hong Kuo, Y. Henry Sun, Joseph Jen-Tse Huang

ACS Applied Materials & Interfaces· Volume 13· Issue 51
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Source abstract

Abstract

Huntington’s disease (HD) belongs to protein misfolding disorders associated with polyglutamine (polyQ)-rich mutant huntingtin (mHtt) protein inclusions. Currently, it is indicated that the aggregation of polyQ-rich mHtt participates in neuronal toxicity and dysfunction. Here, we designed and synthesized a polyglutamine-specific gold nanoparticle (AuNP) complex, which specifically targeted mHtt and alleviated its toxicity. The polyglutamine-specific AuNPs were prepared by decorating the surface of AuNPs with an amphiphilic peptide (JLD1) consisting of both polyglutamine-binding sequences and negatively charged sequences. By applying the polyQ aggregation model system, we demonstrated that AuNPs–JLD1 dissociated the fibrillary aggregates from the polyQ peptide and reduced its β-sheet content in a concentration-dependent manner. By further integrating polyethyleneimine (PEI) onto AuNPs–JLD1, we generated a complex (AuNPs–JLD1–PEI). We showed that this complex could penetrate cells, bind to cytosolic mHtt proteins, dissociate mHtt inclusions, reduce mHtt oligomers, and ameliorate mHtt-induced toxicity. AuNPs–JLD1–PEI was also able to be transported to the brain and improved the functional deterioration in the HD Drosophila larva model. Our results revealed the feasibility of combining AuNPs, JLD1s, and cell-penetrating polymers against mHtt protein aggregation and oligomerization, which hinted on the early therapeutic strategies against HD.
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Research context

PolymersNanomaterials

OpenAlex topics: Genetic Neurodegenerative Diseases · RNA Research and Splicing · Biotin and Related Studies

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Institute of Chemistry, Academia Sinica, No. 128, Sec. 2, Academia Road, Nankang District, Taipei 11529, Taiwan

Sustainable Chemical Science and Technology, Taiwan International Graduate Program, Academia Sinica, No. 128, Sec. 2, Academia Road, Nankang District, Taipei 11529, Taiwan

Department of Applied Chemistry, National Yang Ming Chiao Tung University, Science Building 2, 1001 Ta Hsueh Road, Hsinchu 300, Taiwan

Institute of Molecular Biology, Academia Sinica, No. 128, Sec. 2, Academia Road, Nankang District, Taipei 11529, Taiwan

Chemical Biology and Molecular Biophysics, Taiwan International Graduate Program, Academia Sinica, No. 128, Sec. 2, Academia Road, Nankang District, Taipei 11529, Taiwan

Department and Graduate Institute of Pharmacology, National Taiwan University, 11F, No. 1, Section 1, Ren’ai Road, Zhongzheng District, Taipei 10051, Taiwan

Research Center for Applied Sciences, Academia Sinica, No. 128, Sec. 2, Academia Road, Nankang District, Taipei 115, Taiwan

Department of Applied Chemistry, National Chiayi University, No. 300, University Road, Chiayi 600, Taiwan

Neuroscience Program of Academia Sinica, Academia Sinica, No. 128, Sec. 2, Academia Road, Nankang, Taipei 11529, Taiwan

Funding

Academia Sinica · Ministry of Science and Technology, Taiwan

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