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多药转运体在神经治疗中的作用。

Role of multidrug transporters in neurotherapeutics.

作者信息

Jose Manna, Thomas Sanjeev V

机构信息

Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India.

出版信息

Ann Indian Acad Neurol. 2009 Apr;12(2):89-98. doi: 10.4103/0972-2327.53076.

Abstract

Acquired resistance to antibiotics and other chemotherapeutic agents is a major problem in the practice of neurology and other branches of medicine. There are several mechanisms by which drug resistance is acquired. Multidrug transporters are important glycoproteins located in the cell membrane that actively transport small lipophilic molecules from one side of the cell membrane to the other, most often from the inside to the outside of a cell. They have important protective role yet may prove inconvenient in chemotherapy. In epilepsy and other disorders this mechanism augments the elimination of drugs from their target cells and leads to drug resistance. In this review, we have discussed the biochemical characteristics of multidrug transporters and the mechanisms by which these membrane bound proteins transport their target molecules from one side to the other side of the cell membrane. We have also briefly discussed the application of this knowledge in the understanding of drug resistance in various clinical situations with particular reference to neurological disorders. These proteins located in the placenta have important role in preventing the transplacental movement of drugs in to the fetus which may result in congenital malformations or other defects. The molecular genetic mechanisms that govern the expression of these important proteins are discussed briefly. The potential scope to develop targeted chemotherapeutic agents is also discussed.

摘要

获得性抗生素耐药性和对其他化疗药物的耐药性是神经病学及其他医学分支实践中的一个主要问题。获得耐药性有多种机制。多药转运蛋白是位于细胞膜上的重要糖蛋白,可将亲脂性小分子从细胞膜的一侧主动转运至另一侧,多数情况下是从细胞内转运至细胞外。它们具有重要的保护作用,但在化疗中可能会带来不便。在癫痫及其他疾病中,这种机制会增强药物从其靶细胞中的清除,从而导致耐药性。在本综述中,我们讨论了多药转运蛋白的生化特性以及这些膜结合蛋白将其靶分子从细胞膜一侧转运至另一侧的机制。我们还简要讨论了这一知识在理解各种临床情况下的耐药性方面的应用,特别是针对神经系统疾病。这些位于胎盘的蛋白在防止药物经胎盘进入胎儿体内方面具有重要作用,否则可能导致先天性畸形或其他缺陷。本文还简要讨论了调控这些重要蛋白表达的分子遗传机制。同时也讨论了开发靶向化疗药物的潜在范围。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1ed/2812747/2439acec4279/AIAN-12-89-g001.jpg

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