Glutathione transferases: substrates, inihibitors and pro-drugs in cancer and neurodegenerative diseases.
Glutathione transferases: substrates, inihibitors and pro-drugs in cancer and neurodegenerative diseases.
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DOI：
10.1038/s41389-017-0025-3
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发表时间：
2018-01-24
期刊：
影响因子：
6.2
通讯作者：
Federici L
中科院分区：
文献类型：
--
作者：
Allocati N;Masulli M;Di Ilio C;Federici L
谷胱甘肽转移酶经典的GSH结合活性在细胞对外源性物质和有毒化合物以及抗氧化应激的解毒中起关键作用。然而，癌细胞也利用这一特征来获得耐药性并提高其存活率。结果，发现该家族的各种成员在许多不同的癌症中过度表达。此外，几个GST多态性，从空表型到点突变，在家庭成员中检测到，并发现与神经退行性疾病的发病相关。在过去的几十年里，大量的研究旨在阐明GST在耐药性中所起的作用，开发抑制剂以抵消这种活性，以及利用GST在癌细胞中的前药特异性活化。在这里，我们总结了一些最重要的成就，在这个充满活力的研究领域。
Glutathione transferase classical GSH conjugation activity plays a critical role in cellular detoxification against xenobiotics and noxious compounds as well as against oxidative stress. However, this feature is also exploited by cancer cells to acquire drug resistance and improve their survival. As a result, various members of the family were found overexpressed in a number of different cancers. Moreover several GST polymorphisms, ranging from null phenotypes to point mutations, were detected in members of the family and found to correlate with the onset of neuro-degenerative diseases. In the last decades, a great deal of research aimed at clarifying the role played by GSTs in drug resistance, at developing inhibitors to counteract this activity but also at exploiting GSTs for prodrugs specific activation in cancer cells. Here we summarize some of the most important achievements reached in this lively area of research.
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