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浙江大学学报（医学版）
浙江大学学报（医学版）  2021, Vol. 50 Issue (2): 267-276    DOI: 10.3724/zdxbyxb-2021-0110
综述     
瞬时受体电位 M2 型离子通道在神经系统疾病中的作用研究进展
应颖超(),江佩芳()
浙江大学医学院附属儿童医院神经内科，浙江 杭州 310052
Research progress on transient receptor potential melastatin 2 channel in nervous system diseases
YING Yingchao(),JIANG Peifang()
Department of Neurology, the Children’s Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China
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摘要：

瞬时受体电位 M2 型（TRPM2）离子通道是可渗透钙离子的非选择性阳离子通道，在神经炎症、缺血再灌注脑损伤、神经退行性病变、神经病理性疼痛、癫痫等多种神经系统疾病中发挥重要作用。在缺血再灌注脑损伤中，TRPM2 通过调节谷氨酸离子 N-甲基-D-天冬氨酸受体不同亚基、响应钙离子/锌离子信号，介导神经元死亡。在阿尔茨海默病中，TRPM2 被β-淀粉样肽生成的活性氧激活形成恶性正反馈循环诱导神经元死亡，并在胶质细胞中通过促进炎症反应和氧化应激参与其病理过程。在癫痫中，TRPM2 基因敲除通过抑制自噬和凋亡相关蛋白，减轻癫痫引起的神经元变性。本文总结了近年来 TRPM2 通道在多种中枢神经系统疾病发病机制中的作用及其潜在的药物研发和临床应用前景。
关键词： 瞬时受体电位 M2 型;  神经系统疾病;  缺血再灌注脑损伤;  阿尔茨海默病;  癫痫;  青少年肌阵挛癫痫;  综述    
Abstract:

Transient receptor potential M2 (TRPM2) ion channel is a non-selective cationic channel that can permeate calcium ions, and plays an important role in neuroinflammation, ischemic reperfusion brain injury, neurodegenerative disease, neuropathic pain, epilepsy and other neurological diseases. In ischemic reperfusion brain injury, TRPM2 mediates neuronal death by modulating the different subunits of glutamate N-methyl-D-aspartic acid receptor in response to calcium/zinc signal. In Alzheimer’s disease, TRPM2 is activated by reactive oxygen species generated by β-amyloid peptide to form a malignant positive feedback loop that induces neuronal death and is involved in the pathological process of glial cells by promoting inflammatory response and oxidative stress. In epilepsy, the TRPM2-knockout alleviates epilepsy induced neuronal degeneration by inhibiting autophagy and apoptosis related proteins. The roles of TRPM2 channel in the pathogenesis of various central nervous system diseases and its potential drug development and clinical application prospects are summarized in this review.
Key words: Transient receptor potential melastain 2    Nervous system diseases    Ischemia-reperfusion brain injury    Alzheimer’s disease    Epilepsy    Juvenile myoclonic epilepsy    Review
收稿日期: 2020-10-15 出版日期: 2021-06-18
CLC:  R741  
基金资助: 国家自然科学基金（81671287）
通讯作者: 江佩芳     E-mail: yyc123@zju.edu.cn;jiangpeifang@zju.edu.cn
作者简介: 应颖超，硕士研究生，主要从事儿童神经系统疾病研究；E-mail：yyc123@zju.edu.cn；https：//orcid.org/0000-0002-0856-3962
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引用本文:

应颖超,江佩芳. 瞬时受体电位 M2 型离子通道在神经系统疾病中的作用研究进展[J]. 浙江大学学报（医学版）, 2021, 50(2): 267-276.

YING Yingchao,JIANG Peifang. Research progress on transient receptor potential melastatin 2 channel in nervous system diseases. J Zhejiang Univ (Med Sci), 2021, 50(2): 267-276.

链接本文:

http://www.zjujournals.com/med/CN/10.3724/zdxbyxb-2021-0110    或    http://www.zjujournals.com/med/CN/Y2021/V50/I2/267

图 1  N-甲基-D-天冬氨酸受体相关 TRPM2 通道介导缺血再灌注脑损伤的机制TRPM2 的表达可以促进 PSD-95 表达，抑制 NMDA 受体 GluN2A 亚基；当 PSD-95 激活 GluN2B 时，细胞外钙离子内流，导致 ERK1/2 磷酸化受到抑制，从而促进细胞死亡；抑制 GluN2A 表达可减少突触钙离子内流，并阻止下游 MAPKK 和 PI3K 的激活；Akt 的磷酸化可以抑制促凋亡因子 GSK-3β. 实线箭头代表激活，虚线箭头代表减弱，虚线T型线代表抑制，空心箭头向上代表增加，空心箭头向下代表减少. TRPM2：瞬时受体电位 M2 型；GluN：谷氨酸离子受体 NMDAR 的亚基；PSD：突触后致密区；ERK：胞外信号调节激酶；MAPKK：促分裂原活化的蛋白激酶激酶；PI3K：磷脂酰肌醇 3-激酶；Akt：蛋白激酶 B；GSK：糖原合成酶激酶.
图 2  不同类型神经系统疾病中 TRPM2 引发神经元死亡的共同机制不同类型神经系统疾病（缺血再灌注脑损伤、阿尔茨海默病）中，由于活性氧生成，激活 TRPM2，引起钙离子内流；溶酶体功能障碍释放锌离子，线粒体内锌离子增加，导致线粒体功能障碍，释放活性氧，形成恶性正反馈循环，导致神经元死亡. 其中，大量活性氧可导致 DNA 损伤并激活 PARP 和 PARG；PARP 和 PARG 通过协同作用将烟酰胺腺嘌呤二核苷酸转化为 ADPR 的聚合物，随后将其降解为 ADPR 单体；ADPR 单体充当细胞内配体激活 TRPM2 通道. 实线箭头代表激活，虚线代表解释说明. TRPM2：瞬时受体电位 M2 型；ADPR：腺苷二磷酸核糖；PARP：聚 ADPR 聚合酶；PARG：聚 ADPR 糖水解酶.
1 MALKOP, SYED MORTADZAS A, MCWILLIAMJ, et al.TRPM2 channel in microglia as a new player in neuroinflammation associated with a spectrum of central nervous system pathologies[J]Front pharmacol, 2019, 239.
doi: 10.3389/fphar.2019.00239
2 XIEY F, BELROSEJ C, LEIG, et al.Dependence of NMDA/GSK-3β mediated metaplasticity on TRPM2 channels at hippocampal CA3-CA1 synapses[J]Mol Brain, 2011, 4( 1): 44.
doi: 10.1186/1756-6606-4-44
3 JANGY, LEES H, LEEB, et al.TRPM2, a susceptibility gene for bipolar disorder, regulates glycogen synthase kinase-3 activity in the brain[J]J Neurosci, 2015, 35( 34): 11811-11823.
doi: 10.1523/JNEUROSCI.5251-14.2015
4 BAIJ Z, LIPSKIJ. Differential expression of TRPM2 and TRPV4 channels and their potential role in oxidative stress-induced cell death in organotypic hippocampal culture[J]NeuroToxicology, 2010, 31( 2): 204-214.
doi: 10.1016/j.neuro.2010.01.001
5 BELROSEJ C, XIEY F, GIERSZEWSKIL J, et al.Loss of glutathione homeostasis associated with neuronal senescence facilitates TRPM2 channel activation in cultured hippocampal pyramidal neurons[J]Mol Brain, 2012, 5( 1): 11.
doi: 10.1186/1756-6606-5-11
6 LIX, JIANGL H. Multiple molecular mechanisms form a positive feedback loop driving amyloid β42 peptide-induced neurotoxicity via activation of the TRPM2 channel in hippocampal neurons[J]Cell Death Dis, 2018, 9( 2): 195.
doi: 10.1038/s41419-018-0270-1
7 KANEKOS, KAWAKAMIS, HARAY, et al.A critical role of TRPM2 in neuronal cell death by hydrogen peroxide[J]J Pharmacol Sci, 2006, 101( 1): 66-76.
doi: 10.1254/jphs.fp0060128
8 HILLK, TIGUEN J, KELSELLR E, et al.Characterisation of recombinant rat TRPM2 and a TRPM2-like conductance in cultured rat striatal neurones[J]Neuropharmacology, 2006, 50( 1): 89-97.
doi: 10.1016/j.neuropharm.2005.08.021
9 SUNY, SUKUMARANP, SELVARAJS, et al.TRPM2 and a TRPM2-like conductance in cultured rat striatal neurones[J]l, 2018, 55( 1): 409-420.
doi: 10.1007/s12035-016-0338-9
10 CHUNGK K H, FREESTONEP S, LIPSKIJ. Expression and functional properties of TRPM2 channels in dopaminergic neurons of the substantia nigra of the rat[J]J NeuroPhysiol, 2011, 106( 6): 2865-2875.
doi: 10.1152/jn.00994.2010
11 KRAFTR, GRIMMC, GROSSEK, et al.Hydrogen peroxide and ADP-ribose induce TRPM2-mediated calcium influx and cation currents in microglia[J]Am J Physiol-Cell Physiol, 2004, 286( 1): C129-C137.
doi: 10.1152/ajpcell.00331.2003
12 SMITHM A, HERSONP S, LEEK, et al.Hydrogen peroxide and ADP-ribose induce TRPM2-mediated calcium influx and cation currents in microglia[J]J Physiol, 2003, 547( 2): 417-425.
doi: 10.1113/jphysiol.2002.034561
13 JIANGL H, LIX, SYED MORTADZAS A, et al.The TRPM2 channel nexus from oxidative damage to Alzheimer’s pathologies: an emerging novel intervention target for age-related dementia[J]Ageing Res Rev, 2018, 67-79.
doi: 10.1016/j.arr.2018.07.002
14 OSTAPCHENKOV G, CHENM, GUZMANM S, et al.The transient receptor potential melastatin 2 (TRPM2) channel contributes to β-amyloid oligomer-related neurotoxicity and memory impairment[J]J Neurosci, 2015, 35( 45): 15157-15169.
doi: 10.1523/jneurosci.4081-14.2015
15 KOS Y, WANGS E, LEEH K, et al.Transient receptor potential melastatin 2 governs stress-induced depressive-like behaviors[J]Proc Natl Acad Sci U S A, 2019, 116( 5): 1770-1775.
doi: 10.1073/pnas.1814335116
16 KURINCZUKJ J, WHITE-KONINGM, BADAWIN. Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy[J]Early Hum Dev, 2010, 86( 6): 329-338.
doi: 10.1016/j.earlhumdev.2010.05.010
17 MILLARL J, SHIL, HOERDER-SUABEDISSENA, et al.Neonatal hypoxia ischaemia: mechanisms, models, and therapeutic challenges[J]Front Cell Neurosci, 2017, 78.
doi: 10.3389/fncel.2017.00078
18 JIAJ, VERMAS, NAKAYAMAS, et al.Sex differences in neuroprotection provided by inhibition of TRPM2 channels following experimental stroke[J]J Cereb Blood Flow Metab, 2011, 31( 11): 2160-2168.
doi: 10.1038/jcbfm.2011.77
19 VERMAS, QUILLINANN, YANGY F, et al.TRPM2 channel activation following in vitro ischemia contributes to male hippocampal cell death[J]NeuroSci Lett, 2012, 530( 1): 41-46.
doi: 10.1016/j.neulet.2012.09.044
20 SHIMIZUT, MACEYT A, QUILLINANN, et al.Androgen and PARP-1 regulation of TRPM2 channels after ischemic injury[J]J Cereb Blood Flow Metab, 2013, 33( 10): 1549-1555.
doi: 10.1038/jcbfm.2013.105
21 ALIMI, TEVESL, LIR, et al.Modulation of NMDAR subunit expression by TRPM2 channels regulates neuronal vulnerability to ischemic cell death[J]J Neurosci, 2013, 33( 44): 17264-17277.
doi: 10.1523/jneurosci.1729-13.2013
22 SYED MORTADZAS A, WANGL, LID, et al.TRPM2 channel-mediated ROS-sensitive Ca(2+) signaling mechanisms in immune cells[J]Front Immunol, 2015, 407.
doi: 10.3389/fimmu.2015.00407
23 YEM, YANGW, AINSCOUGHJ F, et al.TRPM2 channel deficiency prevents delayed cytosolic Zn2+ accumulation and CA1 pyramidal neuronal death after transient global ischemia[J/OL]Cell Death Dis, 2014, 5( 11): e1541.
doi: 10.1038/cddis.2014.494
24 ZHANK, YUP, LIUC, et al.Detrimental or beneficial: the role of TRPM2 in ischemia/reperfusion injury[J]Acta Pharmacol Sin, 2016, 37( 1): 4-12.
doi: 10.1038/aps.2015.141
25 LAIT W, ZHANGS, WANGY T. Excitotoxicity and stroke: identifying novel targets for neuroprotection[J]Prog NeuroBiol, 2014, 157-188.
doi: 10.1016/j.pneurobio.2013.11.006
26 MAIC, MANKOOH, WEIL, et al.TRPM2 channel: A novel target for alleviating ischaemia‐reperfusion, chronic cerebral hypo-perfusion and neonatal hypoxic‐ischaemic brain damage[J]J Cell Mol Med, 2020, 24( 1): 4-12.
doi: 10.1111/jcmm.14679
27 ELTZSCHIGH K, ECKLET. Ischemia and reperfusion—from mechanism to translation[J]Nat Med, 2011, 17( 11): 1391-1401.
doi: 10.1038/nm.2507
28 DIETZR M, CRUZ-TORRESI, ORFILAJ E, et al.Reversal of global ischemia-induced cognitive dysfunction by delayed inhibition of TRPM2 ion channels[J]Transl Stroke Res, 2020, 11( 2): 254-266.
doi: 10.1007/s12975-019-00712-z
29 LIX, YANGW, JIANGL H. Alteration in Intracellular Zn2+ homeostasis as a result of TRPM2 channel activation contributes to ROS-induced hippocampal neuronal death[J]Front Mol Neurosci, 2017, 414.
doi: 10.3389/fnmol.2017.00414
30 STORKC J, LIY V. Rising zinc: a significant cause of ischemic neuronal death in the CA1 region of rat hippocampus[J]J Cereb Blood Flow Metab, 2009, 29( 8): 1399-1408.
doi: 10.1038/jcbfm.2009.64
31 SHUTTLEWORTHC W, WEISSJ H. Zinc: new clues to diverse roles in brain ischemia[J]Trends Pharmacol Sci, 2011, 32( 8): 480-486.
doi: 10.1016/j.tips.2011.04.001
32 LIX, JIANGL H. A critical role of the transient receptor potential melastatin 2 channel in a positive feedback mechanism for reactive oxygen species-induced delayed cell death[J]J Cell Physiol, 2019, 234( 4): 3647-3660.
doi: 10.1002/jcp.27134
33 ERKKINENM G, KIMM O, GESCHWINDM D. Clinical neurology and epidemiology of the major neurodegenerative diseases[J]Cold Spring Harb Perspect Biol, 2018, 10( 4): a033118.
doi: 10.1101/cshperspect.a033118
34 HASHIMOTOM, ROCKENSTEINE, CREWSL, et al.Role of protein aggregation in mitochondrial dysfunction and neurodegeneration in Alzheimer’s and Parkinson’s diseases[J]Neuromolecular Med, 2003, 4( 1-2): 21-36.
doi: 10.1385/nmm:4:1-2:21
35 TIRABOSCHIP, HANSENL A, THALL J, et al.The importance of neuritic plaques and tangles to the development and evolution of AD[J]Neurology, 2004, 62( 11): 1984-1989.
doi: 10.1212/01.wnl.0000129697.01779.0a
36 BOURASC, HOFP R, GIANNAKOPOULOSP, et al.Regional distribution of neurofibrillary tangles and senile plaques in the cerebral cortex of elderly patients: a quantitative evaluation of a one-year autopsy population from a geriatric hospital[J]Cereb Cortex, 1994, 4( 2): 138-150.
doi: 10.1093/cercor/4.2.138
37 BACHURINS O, BOVINAE V, USTYUGOVA A. Drugs in clinical trials for Alzheimer’s disease: the major trends[J]Med Res Rev, 2017, 37( 5): 1186-1225.
doi: 10.1002/med.21434
38 BLENNOWK, ZETTERBERGH. Biomarkers for Alzheimer’s disease: current status and prospects for the future[J]J Intern Med, 2018, 284( 6): 643-663.
doi: 10.1111/joim.12816
39 SELKOED J, HARDYJ. The amyloid hypothesis of Alzheimer’s disease at 25 years[J]EMBO Mol Med, 2016, 8( 6): 595-608.
doi: 10.15252/emmm.201606210
40 JANKOWSKYJ L, XUG, FROMHOLTD, et al.Environmental enrichment exacerbates amyloid plaque formation in a transgenic mouse model of Alzheimer disease[J]l, 2003, 62( 12): 1220-1227.
doi: 10.1093/jnen/62.12.1220
41 DE FELICEF G, VELASCOP T, LAMBERTM P, et al.Abeta oligomers induce neuronal oxidative stress through an N-methyl-D-aspartate receptor-dependent mechanism that is blocked by the Alzheimer drug memantine[J]J Biol Chem, 2007, 282( 15): 11590-11601.
doi: 10.1074/jbc.M607483200
42 LAFERLAF M. Calcium dyshomeostasis and intracellular signalling in Alzheimer’s disease[J]Nat Rev Neurosci, 2002, 3( 11): 862-872.
doi: 10.1038/nrn960
43 OLAHM E, JACKSONM F, LIH, et al.Ca2+-dependent induction of TRPM2 currents in hippocampal neurons[J]J Physiol, 2009, 587( 5): 965-979.
doi: 10.1113/jphysiol.2008.162289
44 ?VEY? S, NAZ?RO?LUM. Effects of homocysteine and memantine on oxidative stress related TRP cation channels in in-vitro model of Alzheimer’s disease[J]J Receptor Signal Transduct, 2021, 41( 3): 273-283.
doi: 10.1080/10799893.2020.1806321
45 REGENF, HELLMANN-REGENJ, COSTANTINIE, et al.Neuroinflammation and Alzheimer’s disease: implications for microglial activation[J]Curr Alzheimer Res, 2017, 14( 11): 1140-1148.
doi: 10.2174/1567205014666170203141717
46 AHMADM H, FATIMAM, MONDALA C. Influence of microglia and astrocyte activation in the neuroinflammatory pathogenesis of Alzheimer’s disease: Rational insights for the therapeutic approaches[J]J Clin Neurosci, 2019, 6-11.
doi: 10.1016/j.jocn.2018.10.034
47 WANGJ, JACKSONM F, XIEY F. Glia and TRPM2 channels in plasticity of central nervous system and Alzheimer’s diseases[J]Neural Plast, 2016, 168-0905.
doi: 10.1155/2016/1680905
48 LEEM, CHOT, JANTARATNOTAIN, et al.Depletion of GSH in glial cells induces neurotoxicity: relevance to aging and degenerative neurological diseases[J]FASEB J, 2010, 24( 7): 2533-2545.
doi: 10.1096/fj.09-149997
49 SAHARANS, MANDALP K. The emerging role of glutathione in Alzheimer’s disease[J]J Alzheimer Dis, 2014, 40( 3): 519-529.
doi: 10.3233/jad-132483
50 CALHOUNJ D, HUFFMANA M, BELLINSKII, et al.CACNA1H variants are not a cause of monogenic epilepsy[J]Human Mutat, 2020, 41( 6): 1138-1144.
doi: 10.1002/humu.24017
51 DANIILG, FERNANDES-ROSAF L, CHEMINJ, et al.CACNA1H mutations are associated with different forms of primary aldosteronism[J]EBioMedicine, 2016, 225-236.
doi: 10.1016/j.ebiom.2016.10.002
52 LEMKEJ R, LALD, REINTHALERE M, et al.Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes[J]Nat Genet, 2013, 45( 9): 1067-1072.
doi: 10.1038/ng.2728
53 VIEIRAM M, NGUYENT A, WUK, et al.An epilepsy-associated GRIN2A rare variant disrupts CaMKIIα phosphorylation of GluN2A and NMDA receptor trafficking[J]Cell Rep, 2020, 32( 9): 108104.
doi: 10.1016/j.celrep.2020.108104
54 JANGY, LEEB, KIMH, et al.Trpm2 ablation accelerates protein aggregation by impaired ADPR and autophagic clearance in the brain[J]Mol Neurobiol, 2019, 56( 5): 3819-3832.
doi: 10.1007/s12035-018-1309-0
55 HUH, ZHUT, GONGL, et al.Transient receptor potential melastatin 2 contributes to neuroinflammation and negatively regulates cognitive outcomes in a pilocarpine-induced mouse model of epilepsy[J]Int ImmunoPharmacol, 2020, 106824.
doi: 10.1016/j.intimp.2020.106824
56 ZHENGQ, ZHUT, HUH, et al.TRPM2 ion channel is involved in the aggravation of cognitive impairment and down regulation of epilepsy threshold in pentylenetetrazole-induced kindling mice[J]Brain Res Bull, 2020, 48-60.
doi: 10.1016/j.brainresbull.2019.11.018
57 VANDE VELDEC, CIZEAUJ, DUBIKD, et al.BNIP3 and genetic control of necrosis-like cell death through the mitochondrial permeability transition pore[J]Mol Cell Biol, 2000, 20( 15): 5454-5468.
doi: 10.1128/mcb.20.15.5454-5468.2000
58 SUSINS A, LORENZOH K, ZAMZAMIN, et al.Molecular characterization of mitochondrial apoptosis-inducing factor[J]Nature, 1999, 397( 6718): 441-446.
doi: 10.1038/17135
59 ZHUT, ZHAOY, HUH, et al.TRPM2 channel regulates cytokines production in astrocytes and aggravates brain disorder during lipopolysaccharide-induced endotoxin sepsis[J]Int ImmunoPharmacol, 2019, 105836.
doi: 10.1016/j.intimp.2019.105836
60 BAILEYJ N, PATTERSONC, DE NIJSL, et al.EFHC1 variants in juvenile myoclonic epilepsy: reanalysis according to NHGRI and ACMG guidelines for assigning disease causality[J]Genet Med, 2017, 19( 2): 144-156.
doi: 10.1038/gim.2016.86
61 SUZUKIT, DELGADO-ESCUETAA V, AGUANK, et al.Mutations in EFHC1 cause juvenile myoclonic epilepsy[J]Nat Genet, 2004, 36( 8): 842-849.
doi: 10.1038/ng1393
62 LOUCKSC M, PARKK, WALKERD S, et al.EFHC1, implicated in juvenile myoclonic epilepsy, functions at the cilium and synapse to modulate dopamine signaling[J/OL]eLife, 2019, e37271.
doi: 10.7554/eLife.37271
63 KATANOM, NUMATAT, AGUANK, et al.The juvenile myoclonic epilepsy-related protein EFHC1 interacts with the redox-sensitive TRPM2 channel linked to cell death[J]Cell Calcium, 2012, 51( 2): 179-185.
doi: 10.1016/j.ceca.2011.12.011
64 MAHMUDAN A, YOKOYAMAS, MUNESUET, et al.One single nucleotide polymorphism of the TRPM2 channel gene identified as a risk factor in bipolar disorder associates with autism spectrum disorder in a Japanese population[J]Diseases, 2020, 8( 1): 4.
doi: 10.3390/diseases8010004
65 BELROSEJ C, JACKSONM F. TRPM2: a candidate therapeutic target for treating neurological diseases[J]Acta Pharmacol Sin, 2018, 39( 5): 722-732.
doi: 10.1038/aps.2018.31
66 HARAGUCHIK, KAWAMOTOA, ISAMIK, et al.TRPM2 contributes to inflammatory and neuropathic pain through the aggravation of pronociceptive inflammatory responses in mice[J]J Neuroscience, 2012, 32( 11): 3931-3941.
doi: 10.1523/JNEUROSCI.4703-11.2012
67 HERMOSURAM C, CUIA M, GOR C V, et al.Altered functional properties of a TRPM2 variant in Guamanian ALS and PD[J]Proc Natl Acad Sci U S A, 2008, 105( 46): 18029-18034.
doi: 10.1073/pnas.0808218105
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