Abstract
The sigma receptors were classified into sigma-1 and sigma-2 receptor based on their different pharmacological profiles. In the past two decades, our understanding of the biological and pharmacological properties of the sigma-1 receptor is increasing; however, little is known about the sigma-2 receptor. Recently, the molecular identity of the sigma-2 receptor has been identified as TMEM97. Although more and more evidence has showed that sigma-2 ligands have the ability to treat cancer and Alzheimer’s disease (AD), the mechanisms connecting these two diseases are unknown. Data obtained over the past few years from human and animal models indicate that cholesterol homeostasis is altered in AD and cancer, underscoring the importance of cholesterol homeostasis in AD and cancer. In this review, based on accumulated evidence, we proposed that the beneficial roles of sigma-2 ligands in cancer and AD might be mediated by their regulation of cholesterol homeostasis.
Highlights
The sigma receptors were identified in 1976 and initially recognized as a member of the opiate receptors; later studies revealed that they were different receptors [1]
Substantial evidence has shown that the sigma-2 receptor/transmembrane protein 97 (TMEM97) is involved in the synthesis of cholesterol
This study indicates that TMEM97/sigma-2–progesterone receptor membrane component 1 (PGRMC1)-low-density lipoprotein receptor (LDLR) trimeric complex might be a potential target to reduce
Summary
The sigma receptors were identified in 1976 and initially recognized as a member of the opiate receptors; later studies revealed that they were different receptors [1]. The definition of a sigma-2/TMEM97 agonist and antagonist remains numerous sigma-2 selective have been developed and characterized by receptor cells To are assays categorized agonists, since siramesine, a commonly accepted sigma-2 agonist, induces undefined. The definition of a molecular sigma-2/TMEM97 agonist and antagonist remains cytotoxicity in cancer cells. Using this approach, sigma-2 ligands have been divided into agonists, cells are categorized as agonists, since siramesine, a commonly accepted sigma-2 agonist, induces action of sigma-2 is not understood. Zeng ligands et al proposed that sigma-2 selective compounds with cytotoxic effects on cancer partial agonists, and antagonists [29].this. 2. The synthesis of of cholesterol by feedback feedbackcontrol control involving sterol regulatory element-binding protein.
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