Sigma non-opioid intracellular receptor 1 (SIGMAR1) (SIGMAR1)

Sigma non-opioid intracellular receptor 1 (SIGMAR1), also known as the Sigma-1 receptor or SR31747A-binding protein 1, is a unique ligand-regulated molecular chaperone primarily localized at the mitochondria-associated membrane (MAM) of the endoplasmic reticulum [6, 11]. It plays a critical role in cellular homeostasis by modulating calcium signaling through interactions with the inositol 1,4,5-trisphosphate receptor (IP3R) and regulating the folding of proteins [6, 12]. SIGMAR1 is highly expressed in the central nervous system and various peripheral tissues, and its dysfunction is implicated in a wide range of conditions, including neurodegenerative diseases like Alzheimer's and ALS, as well as psychiatric disorders and cancer [6, 12, 28]. The receptor is targeted by a diverse array of ligands, including the immunosuppressant and antiproliferative agent SR31747A, which binds with high affinity to inhibit tumor cell growth and modulate immune responses [1, 21, 22]. Therapeutic strategies targeting SIGMAR1 aim to leverage its neuroprotective and chaperone functions to treat neurological deficits or exploit its role in cell proliferation for oncology applications [11, 12, 19].

Other names

SR31747A-binding protein 1SRBP1SR-BP1OPRS1ALS16Sigma-1 receptorSigma-1R

Sigma-1 receptor antagonism (e.g., SR31747A), Sigma-1 receptor agonism (e.g., Fluvoxamine), Chaperone modulation, Ion channel regulation