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A Pipeline to Investigate the Structures and Signaling Pathways of Sphingosine 1-Phosphate Receptors
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Sigma-2 Receptor as a Potential Drug Target
Ai-Fang Chen1, Wen-Hui Ma1, Xiao-Yang Xie1
1School of Pharmacy, Guangdong Medical University, 1 Xincheng Ave, Songshan Lake Technology Park, Dongguan, Guangdong 523808, China.
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.
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