Revisiting the sigma-1 receptor as a biological target to treat affective and cognitive disorders

Sigma-1 receptors are reviewed as a biological drug target for affective (including depression) and cognitive disorders. The review summarizes evidence that sigma-1 receptors are multifunctional proteins in endoplasmic reticulum membranes, involved in cellular signal transduction through interactions with receptors, ion channels, lipids, and kinases. Changes in sigma-1 receptor function or expression are linked to diseases such as depression and memory impairments. Preclinical animal studies are reported to show that targeting sigma-1 receptors may help treat affective and cognitive symptoms, including cognitive decline. The review also notes that sigma-1 receptor ligands have entered clinical trials, supporting the idea that modulation of this target has therapeutic potential.