Rhizolutin, a Novel 7/10/6-Tricyclic Dilactone, Dissociates Misfolded Protein Aggregates and Reduces Apoptosis/Inflammation Associated with Alzheimer's Disease
- Authors
- Kwon, Yun; Shin, Jisu; Nam, Kwangho; An, Joon Soo; Yang, Seung-Hoon; Hong, Seong-Heon; Bae, Munhyung; Moon, Kyuho; Cho, Yakdol; Woo, Jiwan; Park, Keunwan; Kim, Kyeonghwan; Shin, Jongheon; Kim, Byung-Yong; Kim, YoungSoo; Oh, Dong-Chan
- Issue Date
- Dec-2020
- Publisher
- WILEY-V C H VERLAG GMBH
- Keywords
- Alzheimer' s disease; amyloid beta; lactones; natural products; tau protein
- Citation
- ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, v.59, no.51, pp.22994 - 22998
- Journal Title
- ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
- Volume
- 59
- Number
- 51
- Start Page
- 22994
- End Page
- 22998
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/83300
- DOI
- 10.1002/anie.202009294
- ISSN
- 1433-7851
- Abstract
- Rhizolutin (1) was discovered as a natural product of ginseng-rhizosphericStreptomycessp. WON17. Its structure features an unprecedented 7/10/6-tricyclic dilactone carbon skeleton composed of dimethylcyclodecatriene flanked by a 7-membered and a 6-membered lactone ring based on spectroscopic analysis. During an unbiased screening of natural product libraries, this novel compound was found to dissociate amyloid-beta (A beta) plaques and tau tangles, which are key pathological hallmarks of Alzheimer's disease (AD). Rhizolutin treatment of APP/PS1 double transgenic mice with AD significantly dissociated hippocampal plaques. In vitro, rhizolutin substantially decreased A beta-induced apoptosis and inflammation in neuronal and glial cells. Our findings introduce a unique chemical entity that targets A beta and tau concurrently by mimicking misfolded protein clearance mechanisms of immunotherapy, which is prominently investigated in clinical trials.
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