Clermont Université, Université Blaise Pascal, Génétique Reproduction et Développement, BP 10448, F-63000 Clermont-Ferrand, France.
Expert Opin Ther Targets. 2011 Feb;15(2):219-32. doi: 10.1517/14728222.2011.547853. Epub 2011 Jan 5.
Liver X receptors (LXR) are transcription factors that belong to the nuclear receptor superfamily. Natural derivatives of cholesterol, known as oxysterols, have been identified as agonistic ligands of LXR. They are thus mainly considered to be intracellular cholesterol 'sensors' whose activation leads to decreased plasma cholesterol. Their implication in other physiologic processes currently prevents their use as therapeutic targets, because of potentially deleterious side effects.
The various LXR agonists and antagonists, along with the physiological functions of LXR. Putative clinical targets including atherosclerosis, diabetes, Alzheimer's disease, skin disorders, reproductive disorders and cancer.
LXR are promising pharmacological targets because of the high potential to develop ligands owing to the variety of natural or synthetic agonists. Three aspects should be developed to select a LXR-ligand for treatment of human disease: bio-availability; isoform specificity; tissue specificity. This will allow the development of selective liver X modulators (SLiMs). The challenge is to overcome deleterious side effects to establish LXR as new pharmacological targets.
肝 X 受体 (LXR) 是核受体超家族的转录因子。胆固醇的天然衍生物，称为氧化固醇，已被确定为 LXR 的激动剂配体。因此，它们主要被认为是细胞内胆固醇的“传感器”，其激活导致血浆胆固醇降低。由于潜在的有害副作用，它们在其他生理过程中的作用目前阻止了它们被用作治疗靶点。
各种 LXR 激动剂和拮抗剂，以及 LXR 的生理功能。包括动脉粥样硬化、糖尿病、阿尔茨海默病、皮肤疾病、生殖障碍和癌症在内的潜在临床靶点。
由于具有开发各种天然或合成激动剂配体的巨大潜力，LXR 是很有前途的药理靶点。为了治疗人类疾病而选择 LXR-配体，有三个方面需要开发：生物利用度；异构体特异性；组织特异性。这将允许开发选择性肝 X 调节剂 (SLiMs)。挑战在于克服有害的副作用，将 LXR 确立为新的药理靶点。
