Sigma-2 Receptor as a Potential Drug Target

Abstract

Sigma-2 receptor plays key roles in promoting tumor cell apoptosis, enhancing efficacy of anti-tumor drugs, blocking signal transduction controlled by Aβ oligomers, regulating Ca²⁺ homeostasis and protecting nerve cells. Studies indicated that sigma-2 receptor may be closely coupled with ROS, LDL, mTOR, RAS, PLC/PKC, lysosomal autophagy and mitochondrial super oxidative stress. In addition, the high expression of this receptor in proliferating cells and nerve cells indicates that sigma-2 receptor is an ideal molecular target for imaging and therapeutic development for cancer, Alzheimer's disease, schizophrenia and traumatic brain injury. Various sigma-2 agonists have shown promising anticancer activities, while sigma-2 antagonists have displayed neuroprotection and inhibition of Aβ oligomers in the brain of Alzheimer's disease patients. Thus, both sigma-2 agonists and antagonists are potentially useful therapeutics for the management of cancer and neurodegenerative disorders.

Keywords: Alzheimer's disease.; Aβ protein; Sigma-2 receptor; anticancer; biomarker; drug target.