BioTalentum Ltd., H-2100 Gödöllő, Hungary.
Molecular Animal Biotechnology Laboratory, Szent István University, H-2100 Gödöllő, Hungary.
Molecules. 2019 Jul 12;24(14):2546. doi: 10.3390/molecules24142546.
The calcium sensing receptor (CaSR) was first identified in parathyroid glands, and its primary role in controlling systemic calcium homeostasis by the regulation of parathyroid hormone (PTH) secretion has been extensively described in literature. Additionally, the receptor has also been investigated in cells and tissues not directly involved in calcium homeostasis, e.g., the nervous system (NS), where it plays crucial roles in early neural development for the differentiation of neurons and glial cells, as well as in the adult nervous system for synaptic transmission and plasticity. Advances in the knowledge of the CaSR's function in such physiological processes have encouraged researchers to further broaden the receptor's investigation in the neuro-pathological conditions of the NS. Interestingly, pre-clinical data suggest that receptor inhibition by calcilytics might be effective in counteracting the pathomechanism underlying Alzheimer's disease and ischemia, while a CaSR positive modulation with calcimimetics has been proposed as a potential approach for treating neuroblastoma. Importantly, such promising findings led to the repurposing of CaSR modulators as novel pharmacological alternatives for these disorders. Therefore, the aim of this review article is to critically appraise evidence which, so far, has been yielded from the investigation of the role of the CaSR in physiology of the nervous system and to focus on the most recent emerging concepts which have reported the receptor as a therapeutic target for neurodegeneration and neuroblastic tumors.
钙敏感受体 (CaSR) 最初在甲状旁腺中被发现，其通过调节甲状旁腺激素 (PTH) 分泌来控制全身钙稳态的主要作用在文献中已有广泛描述。此外，该受体还在不直接参与钙稳态的细胞和组织中进行了研究，例如神经系统 (NS)，在那里它在神经元和神经胶质细胞的早期神经发育中发挥着至关重要的作用，以及在成年神经系统中发挥着突触传递和可塑性的作用。CaSR 在这些生理过程中的功能的知识的进步促使研究人员进一步拓宽了对 NS 神经病理状况下受体的研究。有趣的是，临床前数据表明，通过钙敏感受体抑制剂抑制受体可能有效对抗阿尔茨海默病和缺血的发病机制，而通过钙调蛋白激动剂对 CaSR 进行正调节已被提议作为治疗神经母细胞瘤的潜在方法。重要的是，这些有前途的发现促使 CaSR 调节剂被重新用作这些疾病的新型药理学替代物。因此，本文的目的是批判性地评估迄今为止从钙敏感受体在神经系统生理学中的作用研究中得出的证据，并重点关注最近报道该受体作为神经退行性变和神经母细胞瘤治疗靶点的新兴概念。
