Rhizolutin, a novel 7/10/6tricyclic dilactone, dissociates misfolded protein aggregates and reduces apoptosis/inflammation associated with Alzheimer’s disease
- Rhizolutin, a novel 7/10/6tricyclic dilactone, dissociates misfolded protein aggregates and reduces apoptosis/inflammation associated with Alzheimer’s disease
- 우지완; 박근완; 조약돌; Yun Kwon; Jisu Shin; Kwangho Nam; Joon Soo An; Seung-Hoon Yang; Seong-Heon Hong; Munhyung Bae; Kyuho Moon; YoungSoo Kim; Byung-Yong Kim; Kyeonghwan Kim; Dong-Chan Oh; Jongheon Shin
- Issue Date
- Angewandte Chemie international edition
- VOL 59, NO 51-22998
- 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-b (Ab) plaques and tau tangles, which are key pathological hallmarks of Alzheimers disease (AD). Rhizolutin treatment of APP/PS1 double transgenic mice with AD significantly dissociated hippocampal plaques. In vitro, rhizolutin substantially decreased Ab-induced apoptosis and inflammation in neuronal and glial cells. Our findings introduce
a unique chemical entity that targets Ab and tau concurrently by mimicking misfolded protein clearance mechanisms of immunotherapy, which is prominently investigated in clinical trials.
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