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 2024-01-19T16:01:03Z 2024-01-19T16:01:03Z 2021-09-02 2020-12-14 1433-7851 https://pubs.kist.re.kr/handle/201004/117686 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. English John Wiley & Sons Ltd. THERMOCHEMISTRY Rhizolutin, a Novel 7/10/6-Tricyclic Dilactone, Dissociates Misfolded Protein Aggregates and Reduces Apoptosis/Inflammation Associated with Alzheimer's Disease Article 10.1002/anie.202009294 1 Angewandte Chemie International Edition, v.59, no.51, pp.22994 - 22998 Angewandte Chemie International Edition 59 51 22994 22998 scie scopus 000574855300001 2-s2.0-85091715584 Chemistry, Multidisciplinary Chemistry Article THERMOCHEMISTRY Alzheimer&apos s disease amyloid beta lactones natural products tau protein