The role of the RANKL/RANK/OPG system in the central nervous systems (CNS).

The receptor-activator of NF-κB ligand (RANKL) and its specific receptor RANK have essential roles in regulating bone metabolism and the immune system. Besides, the RANKL/RANK system plays important roles in multiple physiological and pathophysiological processes such as mammary gland development during pregnancy, cancer development, and bone metastasis. While it has long been known that RANKL and RANK are expressed in the central nervous system (CNS), the physiological roles of RANKL/RANK system in the CNS and the underlying molecular mechanisms have been elucidated recently. Over the last decade, several reports showed that the central RANKL/RANK system plays important roles in regulating body temperature, brain ischemia, autoimmune encephalopathy, feeding behavior, and energy metabolism. In this review, it is provided an updated information regarding the roles of RANKL/RANK system in the CNS.