钙敏感受体激活性和失活性突变所致骨矿代谢异常疾病及治疗

Gain and loss-of-function mutations of calcium-sensing receptor associated bone and mineral metabolic disorders and the therapies

钙敏感受体(calcium-sensing receptor,CaSR)是感知细胞外钙离子浓度,调节甲状旁腺素分泌及尿钙重吸收,维持钙稳态的关键受体。CaSR激活性和失活性突变导致钙调定点的移动,引起相应的钙矿物质代谢异常疾病和骨代谢异常表现。本文综述CaSR突变所致疾病的发病机制、临床表现、治疗策略,通过动物实验模型阐述CaSR的病理生理功能,并探讨针对上述疾病的治疗及CaSR配体药物的研究进展。

Calcium-sensing receptor(CaSR)senses the extracellular calcium concentration,regulates the parathyroid hormone(PTH)secretion,and renal calcium reabsorption,plays an important roles in maintaining the calcium homeostasis.Gain and loss-of-function mutations of CaSR lead to the shift of calcium set-point,and result in the mineral and bone diseases.We reviewed the pathophysiology of diseases associated with activating and inactivating mutations of CaSR,and their clinical characteristics,therapeutic strategy,and animal models.To achieve better understanding of CaSR,the allosteric modulators of CaSR may become promising therapeutic options.