| First Author | Kwon Y | Year | 2020 |
| Journal | Angew Chem Int Ed Engl | Volume | 59 |
| Issue | 51 | Pages | 22994-22998 |
| PubMed ID | 32844539 | Mgi Jnum | J:352664 |
| Mgi Id | MGI:7704301 | Doi | 10.1002/anie.202009294 |
| Citation | Kwon Y, et al. (2020) Rhizolutin, a Novel 7/10/6-Tricyclic Dilactone, Dissociates Misfolded Protein Aggregates and Reduces Apoptosis/Inflammation Associated with Alzheimer's Disease. Angew Chem Int Ed Engl 59(51):22994-22998 |
| abstractText | Rhizolutin (1) was discovered as a natural product of ginseng-rhizospheric Streptomyces sp. 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 (Abeta) 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 Abeta-induced apoptosis and inflammation in neuronal and glial cells. Our findings introduce a unique chemical entity that targets Abeta and tau concurrently by mimicking misfolded protein clearance mechanisms of immunotherapy, which is prominently investigated in clinical trials. |
