RRC ID 36916
著者 Wada S, Kubota Y, Sawa R, Umekita M, Hatano M, Ohba S, Hayashi C, Igarashi M, Nomoto A.
タイトル Novel autophagy inducers lentztrehaloses A, B and C.
ジャーナル J Antibiot (Tokyo)
Abstract Trehalose has widespread use as a sweetener, humectant and stabilizer, and is now attracting attention as a promising candidate for the treatment of neurodegenerative diseases as it is an autophagy inducer and chemical chaperone. However, the bioavailability of trehalose is low because it is digested by the hydrolyzing enzyme trehalase, expressed in the intestine and kidney. Enzyme-stable analogs of trehalose would potentially solve this problem. We have previously reported an enzyme-stable analog of trehalose, lentztrehalose, and herein report two new analogs. The original lentztrehalose has been renamed lentztrehalose A and the analogs named lentztrehaloses B and C. Lentztrehalose B is a di-dehydroxylated analog and lentztrehalose C is a cyclized analog of lentztrehalose A. All the lentztrehaloses are only minimally hydrolyzed by mammalian trehalase. The production of the lentztrehaloses is high in rather dry conditions and low in wet conditions. Lentztrehalose B shows a moderate antioxidative activity. These facts suggest that the lentztrehaloses are produced as humectants or protectants for the producer microorganism under severe environmental conditions. All the lentztrehaloses induce autophagy in human cancer cells at a comparable level to trehalose. Considering the enzyme-stability, these lentztrehaloses can be regarded as promising new drug candidates for the treatment of neurodegenerative diseases and other autophagy-related diseases, such as diabetes, arteriosclerosis, cancer and heart disease.
巻・号 68(8)
ページ 521-9
公開日 2015-8-1
DOI 10.1038/ja.2015.23
PII ja201523
PMID 25757606
PMC PMC4579591
MeSH Autophagy / drug effects* Cell Line, Tumor Cell Survival / drug effects Drug Stability Humans Hydrolysis Molecular Structure Trehalase / metabolism Trehalose / analogs & derivatives* Trehalose / chemistry Trehalose / isolation & purification Trehalose / metabolism
IF 2.668
引用数 8
WOS 分野 PHARMACOLOGY & PHARMACY BIOTECHNOLOGY & APPLIED MICROBIOLOGY MICROBIOLOGY IMMUNOLOGY
リソース情報
ヒト・動物細胞 OVK18(RCB1903)