School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, Australia.
Biochem J. 2011 Aug 15;438(1):e1-3. doi: 10.1042/BJ20110996.
In humans, there are 48 members of the superfamily of nuclear receptors. These ligand-activated transcription factors help to integrate our growth, reproduction and metabolism via environmental, nutritional and intrinsic cues. It is therefore not surprising that nuclear receptors are commonly used as drug targets. However, perhaps in the rush to discover new drugs that target these receptors, we sometimes lose sight of their 'real' physiological ligands. In this issue of the Biochemical Journal Goto et al. present evidence that the isoprenoid FPP (farnesyl pyrophosphate) may be a bona fide ligand for the master controller of adipocyte differentiation PPARγ (peroxisome-proliferator-activated receptor γ). This work has wide-ranging implications not only for obesity and diabetes, but also for osteoporosis and the control of circadian rhythms in which PPARγ also plays an important role.
在人类中，有 48 种核受体超家族成员。这些配体激活的转录因子通过环境、营养和内在线索帮助整合我们的生长、繁殖和代谢。因此，核受体通常被用作药物靶点也就不足为奇了。然而，也许在急于发现靶向这些受体的新药的过程中，我们有时会忽略它们的“真正”生理配体。在本期《生物化学杂志》上，Goto 等人提供了证据，表明类异戊二烯 FPP（法呢基焦磷酸）可能是脂肪细胞分化主控制器 PPARγ（过氧化物酶体增殖物激活受体 γ）的真正配体。这项工作不仅对肥胖和糖尿病具有广泛的影响，而且对骨质疏松症和昼夜节律的控制也具有重要意义，PPARγ 在其中也发挥着重要作用。
