a Department of Pharmacology School of Basic Medical Sciences , Wuhan University , Wuhan , China.
b Center for Pharmacogenetics and Department of Pharmaceutical Sciences , University of Pittsburgh , Pittsburgh , PA , USA.
Drug Metab Rev. 2018 Nov;50(4):407-414. doi: 10.1080/03602532.2018.1554673. Epub 2019 Jan 7.
Nuclear receptors (NRs) belong to a family of ligand-dependent transcription factors. The target genes of NRs include many drug metabolizing enzymes and transporters. The central nervous system (CNS) bears the expression of NRs, drug metabolizing enzymes and transporters. NRs that express in the brain can be divided into three groups according to their characteristics of ligand binding: steroid hormone receptors, non-steroid hormone receptors, and orphan receptors. The NR-mediated regulation of drug metabolizing enzymes and transporters plays important roles in the metabolism and disposition of drugs in the CNS and the penetration of endogenous and exogenous substances through the blood-brain barrier (BBB). NR-mediated regulation of drug metabolizing enzymes and transporters can cause the toxicological effects of xenobiotics in the CNS and also lead to drug resistance in the centrum. The regulatory pathways of drug metabolizing enzymes and transporters can provide new strategies for selective regulation of the BBB permeability and drug metabolism in the brain. This review focuses on the importance of NR-mediated regulation of drug metabolizing enzymes and transporters in the CNS and the implications of this regulation in the therapeutic effect of CNS drugs and CNS side effects of drugs and other xenotoxicants.
核受体（NRs）属于配体依赖性转录因子家族。NRs 的靶基因包括许多药物代谢酶和转运体。中枢神经系统（CNS）表达 NRs、药物代谢酶和转运体。在大脑中表达的 NR 可以根据其配体结合的特点分为三组：甾体激素受体、非甾体激素受体和孤儿受体。NR 介导的药物代谢酶和转运体的调节在 CNS 中药物的代谢和处置以及内源性和外源性物质通过血脑屏障（BBB）的渗透中发挥重要作用。NR 介导的药物代谢酶和转运体的调节可导致 CNS 中外源物质的毒理学效应，也可导致中枢耐药性。药物代谢酶和转运体的调节途径可为选择性调节 BBB 通透性和脑内药物代谢提供新策略。本综述重点介绍了 NR 介导的 CNS 中药物代谢酶和转运体的调节的重要性，以及这种调节对 CNS 药物治疗效果和 CNS 药物及其他外源性毒物的副作用的影响。
