Techniques: new pharmacological perspectives for the leptin receptor

Trends in Pharmacological Sciences
Frank PeelmanRalf Jockers

Abstract

The function of leptin, initially confined to its role in energy homeostasis and obesity, has now expanded to the regulation of reproduction, glucose homeostasis, bone formation, wound healing and the immune system. Both stimulation and inhibition of the molecular target of leptin, the leptin receptor (LR), might find applications in disease treatment. Recent advances in the understanding of LR activation mechanisms have led to the design of LR antagonists. Several assays have been developed for the screening and evaluation of LR ligands. Both the extracellular and the intracellular domains of the LR are potential drug targets. The bioluminescence resonance energy transfer technique can be used to screen for compounds that target the extracellular part of the LR, and we propose that the novel reverse mammalian protein-protein interaction trap technique can be used to screen compounds that affect intracellular aspects of LR signalling. These assays can be easily adapted to other pharmacologically relevant receptors.

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