Sigma-1 and Sigma-2 receptors (Sig1R, σ1 receptor, σ2 receptor)

Sigma-1 and Sigma-2 receptors are non-G protein-coupled membrane-bound proteins with distinct molecular structures and functions. Sigma-1 receptor is a chaperone protein located mainly in the endoplasmic reticulum, modulating cell survival, ion channels, and stress responses, while the Sigma-2 receptor is less well-characterized, with roles in cell proliferation and apoptosis, particularly in cancer. Both receptors are widely distributed in brain and peripheral tissues, and their modulators are being investigated for a range of CNS, psychiatric, and oncologic disorders. Sigma receptors are notable for their ability to bind structurally diverse ligands, and their pharmacological regulation offers significant promise as drug targets for several conditions, especially where current therapies are limited or ineffective.

Other names

Sigma receptorSig1Rσ1 receptorσ2 receptor

Agonists mediate neuroprotection, anti-apoptosis, modulate Ca2+ flux, and allosterically modulate signaling proteins. Antagonists induce pro-apoptosis and cell death, particularly in tumor cells (Sigma-2 ligands). Both receptors also modulate ion channel function, including NMDA receptor potentiation and SK channel blockade, and influence ER-mitochondrial signaling.