Center for Biosciences, Department of Biosciences and Nutrition, Karolinska Institutet, S-14183 Stockholm, Sweden.
Trends Pharmacol Sci. 2012 Jul;33(7):394-404. doi: 10.1016/j.tips.2012.03.013. Epub 2012 Apr 27.
Nuclear receptors (NRs) are master regulators of transcriptional programs that integrate the homeostatic control of almost all biological processes. Their direct mode of ligand regulation and genome interaction is at the core of modern pharmacology. The two liver X receptors LXRα and LXRβ are among the emerging newer drug targets within the NR family. LXRs are best known as nuclear oxysterol receptors and physiological regulators of lipid and cholesterol metabolism that also act in an anti-inflammatory way. Because LXRs control diverse pathways in development, reproduction, metabolism, immunity and inflammation, they have potential as therapeutic targets for diseases as diverse as lipid disorders, atherosclerosis, chronic inflammation, autoimmunity, cancer and neurodegenerative diseases. Recent insights into LXR signaling suggest future targeting strategies aiming at increasing LXR subtype and pathway selectivity. This review discusses the current status of our understanding of LXR biology and pharmacology, with an emphasis on the molecular aspects of LXR signaling that constitute the potential of LXRs as drug targets.
核受体（NRs）是转录程序的主要调节剂，整合了几乎所有生物过程的稳态控制。它们的配体调节和基因组相互作用的直接模式是现代药理学的核心。两种肝 X 受体 LXRα 和 LXRβ 是 NR 家族中新兴的较新药物靶点之一。LXRs 作为核甾醇受体最为人所知，是脂质和胆固醇代谢的生理性调节剂，也具有抗炎作用。由于 LXR 控制着发育、生殖、代谢、免疫和炎症等多种途径，它们有可能成为脂质紊乱、动脉粥样硬化、慢性炎症、自身免疫、癌症和神经退行性疾病等多种疾病的治疗靶点。最近对 LXR 信号的深入了解表明，未来的靶向策略旨在提高 LXR 亚型和途径的选择性。这篇综述讨论了我们对 LXR 生物学和药理学的理解现状，重点介绍了 LXR 信号转导的分子方面，这些方面构成了 LXR 作为药物靶点的潜力。
