Sigma-2 receptor as a potential therapeutic target for treating central nervous system disorders

• 作 者: Kazuki Terada Keisuke Migita Yukari Matsushima Chiaki Kamei
• 机 构: Laboratory of Drug Design and Drug Delivery, Faculty of Pharmaceutical Sciences, Fukuoka University,
• 出 处: 中国神经再生研究（英文版）
• 发表日期: 2019年11期

The sigma receptor (Sig-R) was first reported by Martin et al. (1976) and was initially classified into the opioid receptor family. However, Sig-R was subsequently found to differ from the opioid receptor in various studies including ligand binding assays and autoradiography analysis (Tam and Cook, 1984). Sig-R is widely distributed in tissues such as central nervous, digestive, immune, and endocrine tissues. There are two types of Sig-R: sigma-1 (Sig-1R) and sigma-2 receptors (Sig-2R). Re-cent studies reported that each subtype has distinct cellular and physiological functions. Since Hanner et al. (1996) successfully cloned the Sig-1R gene, the functions of Sig-1R have been wide-ly evaluated in the fields of cell biology, molecular biology, can-cer, immunology, and behavioral neuroscience. Particularly, it has been suggested that Sig-1R activates neurons in the central nervous system (CNS) and contributes to physiological func-tions such as memory and cranial nerve protection. In contrast, Sig-2R has not been cloned. Sig-2R is thought to be involved in cellular processes related to neuropathy, as pharmacological studies suggested that Sig-2R is widely distributed in the CNS. Recently, Alon et al. (2017) identified the gene encoding Sig-2R. This perspective focuses on whether Sig-2R is useful as a ther-apeutic target for CNS disorders such as Alzheimer’s disease, Parkinson’s disease, and depression, based on the structure of Sig-2R and its role in nerve growth.