School of Pharmacy, Guangdong Medical University, 1 Xincheng Ave, Songshan Lake Technology Park, Dongguan, Guangdong 523808, China.
Curr Med Chem. 2021;28(21):4172-4189. doi: 10.2174/0929867327666200902172615.
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 Ca 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.
西格玛-2 受体在促进肿瘤细胞凋亡、增强抗肿瘤药物疗效、阻断 Aβ寡聚体控制的信号转导、调节钙稳态和保护神经细胞方面发挥着关键作用。研究表明，西格玛-2 受体可能与 ROS、LDL、mTOR、RAS、PLC/PKC、溶酶体自噬和线粒体超氧化应激密切相关。此外，该受体在增殖细胞和神经细胞中的高表达表明，西格玛-2 受体是癌症、阿尔茨海默病、精神分裂症和创伤性脑损伤成像和治疗开发的理想分子靶点。各种西格玛-2 激动剂已显示出有希望的抗癌活性，而西格玛-2 拮抗剂在阿尔茨海默病患者的大脑中显示出神经保护和抑制 Aβ 寡聚体的作用。因此，西格玛-2 激动剂和拮抗剂都有可能成为癌症和神经退行性疾病治疗的有效药物。
