中枢σ-2受体对神经精神疾病影响和治疗的研究进展

中国临床药理学与治疗学 ›› 2017, Vol. 22 ›› Issue (2): 210-214.

中枢σ-2受体对神经精神疾病影响和治疗的研究进展

吴艳琴^1,2，江沛³，谭亲友⁴，徐萍^1,2，李焕德^1,2，蔡骅琳^1,2

¹中南大学湘雅二医院药学部，长沙 410011，湖南； ²中南大学临床药学研究所，长沙 410011，湖南； ³济宁医学院济宁市第一人民医院，济宁 272000，湖南；4桂林医学院附属医院，桂林 541001，广西

收稿日期:2016-07-13 修回日期:2016-12-05 出版日期:2017-02-26 发布日期:2017-03-02
通讯作者: 蔡骅琳，男，主管药师，硕士生导师，研究方向：精神药理学。 Tel:0731-85292099 E-mail:caihualin1984@163.com
作者简介:吴艳琴，女，硕士研究生，研究方向：临床药学。 Tel:0731-85292099 E-mail:wuyanqin1992@163.com
基金资助:
国家自然科学基金青年基金项目(81401113，81602846，81101001)；国家自然科学基金地区基金项目(81360665)；国家教育部博士点新教师类基金项目(20130162120060)

Research advance of central σ-2 receptor on the pathogenesis and therapeutics of neuropsychiatric diseases

WU Yanqin ^1,2, JIANG Pei ³, TAN Qinyou ⁴, XU Ping ^1,2, LI Huande^1,2, CAI Hualin ^1,2

¹Department of Pharmacy, the Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China; ² Institute of Clinical Pharmacy, Central South University, Changsha 410011, Hunan, China; ³The First People's Hospital of Jining, Jining Medical University, Jining 272000，Hunan, China; ⁴Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi, China

Received:2016-07-13 Revised:2016-12-05 Online:2017-02-26 Published:2017-03-02

摘要/Abstract

摘要：

中枢σ-2 受体可能在神经精神疾病的发病和治疗中起重要作用。近年来，随着新型σ-2受体选择性配体的问世，其神经生物学相关研究取得了长足进展。最新研究发现，孕激素受体膜组分1（progesterone receptor membrane component 1,PGRMC1）可能是σ-2受体的一部分，这为σ-2受体的功能研究提供了新方向。因此，本文就σ-2受体在神经系统中的生理功能，以及σ-2受体对神经精神疾病的影响和治疗的相关研究进展作一综述。

关键词: σ-2受体, 孕激素受体膜组分1, 神经精神疾病

Abstract:

Recent studies indicated that the central σ-2 receptor may play an important role in the pathogenesis and therapeutics of neuropsychiatric diseases. In the recent years, its neurobiological functions have attracted great attention with the emergence of available new selective σ-2 receptor ligands. Several new studies suggest that σ-2 receptor is a part of PGRMC1, shading new light on and direction for the function investigation of σ-2 receptor. Thus, in this review, the physiological functions of σ-2 receptor in the central nervous system, and the involvement of σ-2 receptor in various neuropsychiatric diseases and related treatment are discussed.

Key words: σ-2 receptor, PGRMC1, neuropsychiatric diseases

中图分类号:

R741
R749

吴艳琴，江沛，谭亲友，徐萍，李焕德，蔡骅琳. 中枢σ-2受体对神经精神疾病影响和治疗的研究进展[J]. 中国临床药理学与治疗学, 2017, 22(2): 210-214.

WU Yanqin, JIANG Pei, TAN Qinyou, XU Ping, LI Huande, CAI Hualin. Research advance of central σ-2 receptor on the pathogenesis and therapeutics of neuropsychiatric diseases[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(2): 210-214.

参考文献

［1］张媛, 孙佳锐, 刘玉秋, 等. Sigma受体拮抗剂在治疗成瘾性药物滥用致神经毒性中的研究进展［J］. 中国药科大学学报, 2014, 45(3):253-258.
［2］Xu J, Zeng C, Chu W, et al. Identification of the PGRMC1 protein complex as the putative sigma-2 receptor binding site［J］. Nat Comms, 2011, 2:380.
［3］Ahmed ISA,Chamberlain C,Craven RJ.S2RPgrmc1:the cytochrome-related sigma-2 receptor that regulates lipid and drug metabolism and hormone signaling［J］.Expert Opin Drug Met,2012,8(3):361-370.
［4］Izzo NJ, Staniszewski A, To L, et al. Alzheimer's therapeutics targeting amyloid beta 1-42 oligomers I: Abeta 42 oligomer binding to specific neuronal receptors is displaced by drug candidates that improve cognitive deficits［J］. Plos One, 2014, 9(11):e111898.
［5］Cassano G, Gasparre G, Niso M, et al. F281, synthetic agonist of the sigma-2 receptor, induces Ca2+ efflux from the endoplasmic reticulum and mitochondria in SK-N-SH cells［J］. Cell Calcium, 2009, 45(4):340-345.
［6］Cassano G, Gasparre G, Contino M, et al. The sigma-2 receptor agonist PB28 inhibits calcium release from the endoplasmic reticulum of SK-N-SH neuroblastoma cells［J］. Cell Calcium, 2006, 40(1):23-28.
［7］Su TP, Hayashi T, Maurice T. G-Protein-linked L-type Ca2+ channels on plasma membranes and IP 3 receptors on endoplasmic reticulum in NG-108 cells are regulated by σ 1 receptors: Ca2+ mobilization and σ 1 receptor antisense studies［J］. Coc Neurosci Abstr, 1998, 24:2055.
［8］Spruce BA, Campbell LA, McTavish N, et al. Small molecule antagonists of the sigma-1 receptor cause selective release of the death program in tumor and self-reliant cells and inhibit tumor growth in vitro and in vivo［J］. Cancer Res, 2004, 64(14):4875-4886.
［9］Wheeler KT, Wang LM, Wallen CA, et al. Sigma-2 receptors as a biomarker of proliferation in solid tumours［J］. Br J Cancer, 2000, 82(6):1223-1232.
［10］Garces-Ramirez L, Green JL, Hiranita T, et al. Sigma receptor agonists: receptor binding and effects on mesolimbic dopamine neurotransmission assessed by microdialysis［J］. Biol Psychiatry, 2011, 69(3):208-217.
［11］Miller GM. The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity［J］. J Neurochem, 2011, 116(2):164-176.
［12］Iniguez MA, Punzon C, Nieto R, et al. Inhibitory effects of sigma-2 receptor agonists on T lymphocyte activation［J］. Front Pharmacol, 2013, 4:23.
［13］Pluchino N, Russo M, Santoro AN, et al. Steroid hormones and BDNF［J］. Neuroscience, 2013, 239:271-279.
［14］Morita K, Her S. Progesterone pretreatment enhances serotonin-stimulated BDNF gene expression in rat c6 glioma cells through production of 5alpha-reduced neurosteroids［J］. J Mol Neurosci, 2008, 34(3):193-200.
［15］De Nicola AF, Labombarda F, Gonzalez DM, et al. Progesterone neuroprotection in traumatic CNS injury and motoneuron degeneration［J］. Front Neuroendocrinol, 2009, 30(2):173-187.
［16］Su C, Cunningham RL, Rybalchenko N, et al. Progesterone increases the release of brain-derived neurotrophic factor from glia via progesterone receptor membrane component 1 (Pgrmc1)-dependent ERK5 signaling［J］. Endocrinology, 2012, 153(9):4389-4400.
［17］Izzo NJ, Xu J, Zeng C, et al. Alzheimer's therapeutics targeting amyloid beta 1-42 oligomers II: Sigma-2/PGRMC1 receptors mediate Abeta 42 oligomer binding and synaptotoxicity［J］. Plos One, 2014, 9(11):e111899.
［18］Takahashi M, Hayashi H, Watanabe Y, et al. Diagnostic classification of schizophrenia by neural network analysis of blood-based gene expression signatures［J］. Schizophr Res, 2010, 119(1-3):210-218.
［19］Tam SW, Cook L. Sigma opiates and certain antipsychotic drugs mutually inhibit (+)-［3H］ SKF 10,047 and ［3H］haloperidol binding in guinea pig brain membranes［J］. Proc Natl Acad Sci U S A, 1984, 81(17):5618-5621.
［20］Bowen WD, Moses EL, Tolentino PJ, et al. Metabolites of haloperidol display preferential activity at sigma receptors compared to dopamine D-2 receptors［J］. Eur J Pharmacol, 1990, 177(3):111-118.
［21］Wei Z, Mousseau DD, Dai Y, et al. Haloperidol induces apoptosis via the sigma2 receptor system and Bcl-XS［J］. Pharmacogenomics J, 2006, 6(4):279-288.
［22］Cai HL, Tan QY, Jiang P, et al. A potential mechanism underlying atypical antipsychotics-induced lipid disturbances［J］. Transl Psychiatry, 2015, 5(10):e661.
［23］Bermack JE, Debonnel G. The role of sigma receptors in depression［J］. J Pharmacol Sci, 2005, 97(3):317-336.
［24］Sanchez C, Papp M. The selective sigma2 ligand Lu 28-179 has an antidepressant-like profile in the rat chronic mild stress model of depression［J］. Behav Pharmacol, 2000, 11(2):117-124.
［25］Zeng C, Rothfuss JM, Zhang J, et al. Functional assays to define agonists and antagonists of the sigma-2 receptor［J］. Anal Biochem, 2014, 448:68-74.
［26］Sanchez C, Arnt J, Costall B, et al. The selective sigma2-ligand Lu 28-179 has potent anxiolytic-like effects in rodents［J］. J Pharmacol Exp Ther, 1997, 283(3):1323-1332.
［27］金佳利, 刘学源. Sigma-1受体与阿尔茨海默病关系的研究进展［J］. 同济大学学报(医学版), 2015, (5):129-132.
［28］Sun F, Nguyen T, Jin X, et al. Pgrmc1/BDNF Signaling Plays a Critical Role in Mediating Glia-Neuron Crosstalk［J］. Endocrinology, 2016, 157(5): 2067-2079.
［29］Lever JR, Miller DK, Green CL, et al. A selective sigma-2 receptor ligand antagonizes cocaine-induced hyperlocomotion in mice［J］. Synapse, 2014, 68(2):73-84.
［30］Glick SD, Maisonneuve IS. Mechanisms of antiaddictive actions of ibogaine［J］. Ann N Y Acad Sci, 1998, 844:214-226.
［31］Chu UB, Mavlyutov TA, Chu ML, et al. The Sigma-2 Receptor and Progesterone Receptor Membrane Component 1 are Different Binding Sites Derived From Independent Genes［J］. EBio Medicine, 2015, 2(11):1806-1813.
［32］Hiranita T. Identification of the Sigma-2 Receptor: Distinct from the Progesterone Receptor Membrane Component 1 (PGRMC1)［J］. J Alcohol Drug Depend, 2016,4.
［33］Cahill MA, Jazayeri JA, Catalano SM, et al. The emerging role of progesterone receptor membrane component 1 (PGRMC1) in cancer biology［J］. Biochim Biophys Acta, 2016, 1866(2):339-349.