Abstract:

The sigma receptor (Sig-R) was first reported by Martin et al. 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. 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). Recent studies reported that each subtype has distinct cellular and physiological functions. Since Hanner et al. successfully cloned the Sig-1R gene, the functions of Sig-1R have been widely evaluated in the fields of cell biology, molecular biology, cancer, immunology, and behavioral neuroscience. Particularly, it has been suggested that Sig-1R activates neurons in the central nervous system (CNS) and contributes to physiological functions 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. identified the gene encoding Sig-2R. This perspective focuses on whether Sig-2R is useful as a therapeutic 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.