Novel autophagy inducers lentztrehaloses A, B and C.
Novel autophagy inducers lentztrehaloses A, B and C.
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DOI：
10.1038/ja.2015.23
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发表时间：
2015-08
期刊：
影响因子：
--
通讯作者：
Nomoto A
中科院分区：
文献类型：
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作者：
Wada S;Kubota Y;Sawa R;Umekita M;Hatano M;Ohba S;Hayashi C;Igarashi M;Nomoto A
海藻糖广泛用作甜味剂、保湿剂和稳定剂，由于它是自噬诱导剂和化学伴侣，目前作为治疗神经退行性疾病的有前景的候选者而受到关注。然而，海藻糖的生物利用度较低，因为它被肠和肾中表达的水解酶海藻糖酶消化。海藻糖的酶稳定类似物可能会解决这个问题。我们之前报道了海藻糖的酶稳定类似物，lentztrehalose，本文报道了两种新的类似物。最初的慢海藻糖已更名为慢海藻糖 A，类似物命名为慢海藻糖 B 和 C。慢海藻糖 B 是二脱羟基类似物，慢海藻糖 C 是慢海藻糖 A 的环化类似物。所有慢海藻糖仅被哺乳动物最低限度水解。 海藻糖酶。在相当干燥的条件下，慢藻糖的产量较高，在潮湿的条件下产量较低。 Lentztrehalose B 显示出中等的抗氧化活性。这些事实表明，慢藻糖是在恶劣的环境条件下作为生产微生物的保湿剂或保护剂而产生的。所有慢海藻糖均以与海藻糖相当的水平诱导人类癌细胞自噬。考虑到酶的稳定性，这些慢藻糖可被视为治疗神经退行性疾病和其他自噬相关疾病（如糖尿病、动脉硬化、癌症和心脏病）的有前途的新候选药物。
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.