The sigma-1 receptor: roles in neuronal plasticity and disease

Sigma-1 receptors (Sig-1Rs) have been implicated in many neurological and psychiatric conditions. Sig-1Rs are intracellular chaperones that reside specifically at the endoplasmic reticulum (ER)–mitochondrion interface, referred to as the mitochondrion-associated ER membrane (MAM). Here, Sig-1Rs regulate ER–mitochondrion Ca2+ signaling. In this review, we discuss the current understanding of Sig-1R functions. Based on this, we suggest that the key cellular mechanisms linking Sig-1Rs to neurological disorders involve the translocation of Sig-1Rs from the MAM to other parts of the cell, whereby Sig-1Rs bind and modulate the activities of various ion channels, receptors, or kinases. Thus, Sig-1Rs and their associated ligands may represent new avenues for treating aspects of neurological and psychiatric diseases.