Residential College | false |
Status | 已發表Published |
Canthin-6-One Accelerates Alpha-Synuclein Degradation by Enhancing UPS Activity: Drug Target Identification by CRISPR-Cas9 Whole Genome-Wide Screening Technology | |
Ning-Ning Yuan1; Cui-Zan Cai1; Ming-Yue Wu1; Qi Zhu1; HuanXing Su1; Min Li2; JiaoYan Ren3; Jie-Qiong Tan4; Jia-Hong Lu1 | |
2019-01 | |
Source Publication | FRONTIERS IN PHARMACOLOGY |
ISSN | 1663-9812 |
Volume | 10 |
Other Abstract | Parkinson’s disease (PD) is the second most common neurodegenerative disorder characterized by the accumulation of protein aggregates (namely Lewy bodies) in dopaminergic neurons in the substantia nigra region of the brain. Alpha-synuclein (α-syn) is the major component of Lewy bodies in PD patients, and impairment of the ubiquitin-proteasome system has been linked to its accumulation. In this work, we developed a tetracycline–inducible expression system, with simultaneous induced expression of α-syn-EGFP and a bright red fluorescent protein marker (mCherry) to screen for potential compounds for degrading α-syn. We identified canthin-6-one as an α-syn lowering compound which promoted both wild type and mutants α-syn degradation in an ubiquitin-proteasome-system (UPS) dependent manner. By CRISPR/Cas9 genome-wide screening technology, we identified RPN2/PSMD1, the 26S proteasome non-ATPase regulatory subunit 1, as the targeting gene for pharmacological activity of canthin-6-one. Finally, we showed that canthin-6-one up-regulates PSMD1 and enhances UPS function by activating PKA. |
Keyword | Canthin-6-one Parkinson’s Disease Alpha-synuclein Ubiquitin-proteasome-system Crispr/cas9 Rpn2/psmd1 Pka |
DOI | 10.3389/fphar.2019.00016 |
Indexed By | SCIE |
Language | 英語English |
WOS Research Area | Pharmacology & Pharmacy |
WOS Subject | Pharmacology & Pharmacy |
WOS ID | WOS:000456925900001 |
Scopus ID | 2-s2.0-85065338314 |
Fulltext Access | |
Citation statistics | |
Document Type | Journal article |
Collection | Institute of Chinese Medical Sciences |
Corresponding Author | Jie-Qiong Tan; Jia-Hong Lu |
Affiliation | 1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau,Macao, China 2.Mr. and Mrs. Ko Chi Ming Centre for Parkinson’s Disease Research, School of Chinese Medicine,Hong Kong Baptist University, Hong Kong, China 3.School of Food Science and Engineering, South China Universityof Technology, Guangzhou, China 4.Center for Medical Genetics, School of Life Sciences, Central South University,Changsha, China |
First Author Affilication | Institute of Chinese Medical Sciences |
Corresponding Author Affilication | Institute of Chinese Medical Sciences |
Recommended Citation GB/T 7714 | Ning-Ning Yuan,Cui-Zan Cai,Ming-Yue Wu,et al. Canthin-6-One Accelerates Alpha-Synuclein Degradation by Enhancing UPS Activity: Drug Target Identification by CRISPR-Cas9 Whole Genome-Wide Screening Technology[J]. FRONTIERS IN PHARMACOLOGY, 2019, 10. |
APA | Ning-Ning Yuan., Cui-Zan Cai., Ming-Yue Wu., Qi Zhu., HuanXing Su., Min Li., JiaoYan Ren., Jie-Qiong Tan., & Jia-Hong Lu (2019). Canthin-6-One Accelerates Alpha-Synuclein Degradation by Enhancing UPS Activity: Drug Target Identification by CRISPR-Cas9 Whole Genome-Wide Screening Technology. FRONTIERS IN PHARMACOLOGY, 10. |
MLA | Ning-Ning Yuan,et al."Canthin-6-One Accelerates Alpha-Synuclein Degradation by Enhancing UPS Activity: Drug Target Identification by CRISPR-Cas9 Whole Genome-Wide Screening Technology".FRONTIERS IN PHARMACOLOGY 10(2019). |
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