Rectifying Attenuated Store-Operated Calcium Entry as a Therapeutic Approach for Alzheimer’s Disease

doi:10.2174/1567205018666210119150613
摘要

阿尔茨海默氏病（AD）是最常见的神经退行性疾病。尽管已经确定了AD的病理学特征，但是衍生的疗法不能有效地减慢或阻止疾病的进展。因此，其他致病机制可能与AD发病机制有关。在AD患者和许多AD模型中一直观察到细胞内钙（Ca 2+）异位稳态，并且可能在淀粉样斑块和神经原纤维缠结发展之前出现。因此，细胞内Ca 2+破坏被认为在AD发展中起重要作用，并且可以用作有希望的治疗干预靶标。 AD中出现的细胞内Ca2 +信号转导途径破坏之一是减毒的钙操纵性Ca2 +进入（SOCE）。 SOCE是一种细胞外Ca2 +进入机制，主要由细胞内Ca2 +存储耗竭触发。维持正常的SOCE功能不仅为细胞补充ER Ca2 +储存提供了一种手段，而且还可以作为维持正常神经元功能（包括兴奋性，神经发生，神经传递，突触可塑性和基因表达）的细胞信号。但是，正常的SOCE功能在AD中会减弱，从而导致神经元脊柱稳定性和突触可塑性破坏，并促进淀粉样蛋白生成。越来越多的证据表明，纠正神经元SOCE减少可能会干预AD的发展。在这篇综述中，将讨论SOCE破坏的机制以及对AD的相关致病影响。我们还将重点介绍可能有助于改善ADCE治疗中SOCE缺乏症的潜在治疗目标或方法。
关键词: 钙信号传导，阿尔茨海默氏病，储库操作性钙进入，神经发生，淀粉样蛋白形成，神经退行性疾病。
« Previous Next »
[1] 
International, ASD, World Alzheimer report 2019: Attitudes to dementia 2019.
[2] 
Tiraboschi P, Hansen LA, Thal LJ, Corey-Bloom J. The importance of neuritic plaques and tangles to the development and evolution of AD. Neurology  2004; 62(11): 1984-9.
[http://dx.doi.org/10.1212/01.WNL.0000129697.01779.0A] [PMID: 15184601] 
[3] 
Graham WV, Bonito-Oliva A, Sakmar TP. Update on Alzheimer’s disease therapy and prevention strategies. Annu Rev Med  2017; 68(1): 413-30.
[http://dx.doi.org/10.1146/annurev-med-042915-103753] [PMID: 28099083] 
[4] 
Chakroborty S, Stutzmann GE. Calcium channelopathies and Alzheimer’s disease: Insight into therapeutic success and failures. Eur J Pharmacol  2014; 739: 83-95.
[http://dx.doi.org/10.1016/j.ejphar.2013.11.012] [PMID: 24316360] 
[5] 
Anekonda TS, Quinn JF. Calcium channel blocking as a therapeutic strategy for Alzheimer’s disease: the case for isradipine. Biochim Biophys Acta  2011; 1812(12): 1584-90.
[http://dx.doi.org/10.1016/j.bbadis.2011.08.013] [PMID: 21925266] 
[6] 
Toescu EC, Verkhratsky A. The importance of being subtle: Small changes in calcium homeostasis control cognitive decline in normal aging. Aging Cell  2007; 6(3): 267-73.
[http://dx.doi.org/10.1111/j.1474-9726.2007.00296.x] [PMID: 17517038] 
[7] 
LaFerla FM. Calcium dyshomeostasis and intracellular signalling in Alzheimer’s disease. Nat Rev Neurosci  2002; 3(11): 862-72.
[http://dx.doi.org/10.1038/nrn960] [PMID: 12415294] 
[8] 
Raza M, Deshpande LS, Blair RE, Carter DS, Sombati S, DeLorenzo RJ. Aging is associated with elevated intracellular calcium levels and altered calcium homeostatic mechanisms in hippocampal neurons. Neurosci Lett  2007; 418(1): 77-81.
[http://dx.doi.org/10.1016/j.neulet.2007.03.005] [PMID: 17374449] 
[9] 
Querfurth HW, Selkoe DJ. Calcium ionophore increases amyloid beta peptide production by cultured cells. Biochemistry  1994; 33(15): 4550-61.
[http://dx.doi.org/10.1021/bi00181a016] [PMID: 8161510] 
[10] 
Bezprozvanny I, Mattson MP. Neuronal calcium mishandling and the pathogenesis of Alzheimer’s disease. Trends Neurosci  2008; 31(9): 454-63.
[http://dx.doi.org/10.1016/j.tins.2008.06.005] [PMID: 18675468] 
[11] 
Buxbaum JD, Ruefli AA, Parker CA, Cypess AM, Greengard P. Calcium regulates processing of the Alzheimer amyloid protein precursor in a protein kinase C-independent manner. Proc Natl Acad Sci USA  1994; 91(10): 4489-93.
[http://dx.doi.org/10.1073/pnas.91.10.4489] [PMID: 8183935] 
[12] 
Berridge MJ, Lipp P, Bootman MD. The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol  2000; 1(1): 11-21.
[http://dx.doi.org/10.1038/35036035] [PMID: 11413485] 
[13] 
Khachaturian ZS. Calcium hypothesis of Alzheimer’s disease and brain aging. Ann N Y Acad Sci  1994; 747(1): 1-11.
[http://dx.doi.org/10.1111/j.1749-6632.1994.tb44398.x] [PMID: 7847664] 
[14] 
Berridge MJ. Calcium hypothesis of Alzheimer’s disease. Pflugers Arch  2010; 459(3): 441-9.
[http://dx.doi.org/10.1007/s00424-009-0736-1] [PMID: 19795132] 
[15] 
Putney JW Jr. A model for receptor-regulated calcium entry. Cell Calcium  1986; 7(1): 1-12.
[http://dx.doi.org/10.1016/0143-4160(86)90026-6] [PMID: 2420465] 
[16] 
Oritani K, Kincade PW. Identification of stromal cell products that interact with pre-B cells. J Cell Biol  1996; 134(3): 771-82.
[http://dx.doi.org/10.1083/jcb.134.3.771] [PMID: 8707854] 
[17] 
Sabbioni S, Barbanti-Brodano G, Croce CM, Negrini M. GOK: A gene at 11p15 involved in rhabdomyosarcoma and rhabdoid tumor development. Cancer Res  1997; 57(20): 4493-7.
[PMID: 9377559] 
[18] 
Liou J, Kim ML, Heo WD, et al. STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx. Curr Biol  2005; 15(13): 1235-41.
[http://dx.doi.org/10.1016/j.cub.2005.05.055] [PMID: 16005298] 
[19] 
Roos J, DiGregorio PJ, Yeromin AV, et al. STIM1, an essential and conserved component of store-operated Ca2+ channel function. J Cell Biol  2005; 169(3): 435-45.
[http://dx.doi.org/10.1083/jcb.200502019] [PMID: 15866891] 
[20] 
Williams RT, Manji SS, Parker NJ, et al. Identification and characterization of the STIM (stromal interaction molecule) gene family: Coding for a novel class of transmembrane proteins. Biochem J  2001; 357(Pt 3): 673-85.
[http://dx.doi.org/10.1042/bj3570673] [PMID: 11463338] 
[21] 
Stathopulos PB, Zheng L, Li GY, Plevin MJ, Ikura M. Structural and mechanistic insights into STIM1-mediated initiation of store-operated calcium entry. Cell  2008; 135(1): 110-22.
[http://dx.doi.org/10.1016/j.cell.2008.08.006] [PMID: 18854159] 
[22] 
Zheng L, Stathopulos PB, Li GY, Ikura M. Biophysical characterization of the EF-hand and SAM domain containing Ca2+ sensory region of STIM1 and STIM2. Biochem Biophys Res Commun  2008; 369(1): 240-6.
[http://dx.doi.org/10.1016/j.bbrc.2007.12.129] [PMID: 18166150] 
[23] 
Fahrner M, Muik M, Schindl R, et al.  A coiled-coil clamp controls both conformation and clustering of stromal interaction molecule 1 (STIM1)  2014; 289(48): 33231-44.
[24] 
Muik M, Frischauf I, Derler I, et al. Dynamic coupling of the putative coiled-coil domain of ORAI1 with STIM1 mediates ORAI1 channel activation. J Biol Chem  2008; 283(12): 8014-22.
[http://dx.doi.org/10.1074/jbc.M708898200] [PMID: 18187424] 
[25] 
Zhou Y, Mancarella S, Wang Y, et al. The short N-terminal domains of STIM1 and STIM2 control the activation kinetics of Orai1 channels. J Biol Chem  2009; 284(29): 19164-8.
[http://dx.doi.org/10.1074/jbc.C109.010900] [PMID: 19487696] 
[26] 
Brandman O, Liou J, Park WS, Meyer T. STIM2 is a feedback regulator that stabilizes basal cytosolic and endoplasmic reticulum Ca2+ levels. Cell  2007; 131(7): 1327-39.
[http://dx.doi.org/10.1016/j.cell.2007.11.039] [PMID: 18160041] 
[27] 
Zbidi H, Jardin I, Woodard GE, et al. STIM1 and STIM2 are located in the acidic Ca2+ stores and associates with Orai1 upon depletion of the acidic stores in human platelets. J Biol Chem  2011; 286(14): 12257-70.
[http://dx.doi.org/10.1074/jbc.M110.190694] [PMID: 21321120] 
[28] 
Vig M, Peinelt C, Beck A, et al. CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry. Science  2006; 312(5777): 1220-3.
[http://dx.doi.org/10.1126/science.1127883] [PMID: 16645049] 
[29] 
Feske S, Gwack Y, Prakriya M, et al. A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function. Nature  2006; 441(7090): 179-85.
[http://dx.doi.org/10.1038/nature04702] [PMID: 16582901] 
[30] 
Stanisz H, Schwarz EC, Müller CSL, et al. ORAI1 Ca2+ channels control endothelin-1-induced mitogenesis and melanogenesis in primary human melanocytes  2012; 132(5): 1443-51.
[31] 
Mignen O, Thompson JL, Shuttleworth TJ. The molecular architecture of the arachidonate-regulated Ca2+-selective ARC channel is a pentameric assembly of Orai1 and Orai3 subunits. J Physiol  2009; 587(Pt 17): 4181-97.
[http://dx.doi.org/10.1113/jphysiol.2009.174193] [PMID: 19622606] 
[32] 
Maruyama Y, Ogura T, Mio K, et al. Tetrameric Orai1 is a teardrop-shaped molecule with a long, tapered cytoplasmic domain. J Biol Chem  2009; 284(20): 13676-85.
[http://dx.doi.org/10.1074/jbc.M900812200] [PMID: 19289460] 
[33] 
Hou X, Pedi L, Diver MM, Long SB. Crystal structure of the calcium release-activated calcium channel Orai. Science  2012; 338(6112): 1308-13.
[http://dx.doi.org/10.1126/science.1228757] [PMID: 23180775] 
[34] 
Cai X, Zhou Y, Nwokonko RM, et al. The Orai1 store-operated calcium channel functions as a hexamer. J Biol Chem  2016; 291(50): 25764-75.
[http://dx.doi.org/10.1074/jbc.M116.758813] [PMID: 27780862] 
[35] 
Cheng KT, Ong HL, Liu X, Ambudkar IS. Contribution and regulation of TRPC channels in store-operated Ca2+ entry. Curr Top Membr  2013; 71: 149-79.
[36] 
Zhu X, Jiang M, Peyton M, et al. Trp, a novel mammalian gene family essential for agonist-activated capacitative Ca2+ entry. Cell  1996; 85(5): 661-71.
[http://dx.doi.org/10.1016/S0092-8674(00)81233-7] [PMID: 8646775] 
[37] 
Cosens DJ, Manning A. Abnormal electroretinogram from a Drosophila mutant. Nature  1969; 224(5216): 285-7.
[http://dx.doi.org/10.1038/224285a0] [PMID: 5344615] 
[38] 
Minke B, Wu C, Pak WL. Induction of photoreceptor voltage noise in the dark in Drosophila mutant. Nature  1975; 258(5530): 84-7.
[http://dx.doi.org/10.1038/258084a0] [PMID: 810728] 
[39] 
Wes PD, Chevesich J, Jeromin A, Rosenberg C, Stetten G, Montell C. TRPC1, a human homolog of a Drosophila store-operated channel. Proc Natl Acad Sci USA  1995; 92(21): 9652-6.
[http://dx.doi.org/10.1073/pnas.92.21.9652] [PMID: 7568191] 
[40] 
Zhu X, Chu PB, Peyton M, Birnbaumer L. Molecular cloning of a widely expressed human homologue for the Drosophila trp gene. FEBS Lett  1995; 373(3): 193-8.
[http://dx.doi.org/10.1016/0014-5793(95)01038-G] [PMID: 7589464] 
[41] 
Gees M, Colsoul B, Nilius B. The role of transient receptor potential cation channels in Ca2+ signaling. Cold Spring Harb Perspect Biol  2010; 2(10): a003962-2.
[http://dx.doi.org/10.1101/cshperspect.a003962] [PMID: 20861159] 
[42] 
Zitt C, Zobel A, Obukhov AG, et al. Cloning and functional expression of a human Ca2+-permeable cation channel activated by calcium store depletion. Neuron  1996; 16(6): 1189-96.
[http://dx.doi.org/10.1016/S0896-6273(00)80145-2] [PMID: 8663995] 
[43] 
BROUGH. Contribution of endogenously expressed Trp1 to a Ca2+-selective, store-operated Ca2+ entry pathway. FASEB J  2001; 15(10): 1727-38.
[PMID: 11481250] 
[44] 
Rosado JA, Brownlow SL, Sage SO. Endogenously expressed Trp1 is involved in store-mediated Ca2+ entry by conformational coupling in human platelets. J Biol Chem  2002; 277(44): 42157-63.
[http://dx.doi.org/10.1074/jbc.M207320200] [PMID: 12196544] 
[45] 
Liu X, Wang W, Singh BB, et al. Trp1, a candidate protein for the store-operated Ca2+ influx mechanism in salivary gland cells. J Biol Chem  2000; 275(5): 3403-11.
[http://dx.doi.org/10.1074/jbc.275.5.3403] [PMID: 10652333] 
[46] 
Worley PF, Zeng W, Huang GN, et al. TRPC channels as STIM1-regulated store-operated channels. Cell Calcium  2007; 42(2): 205-11.
[http://dx.doi.org/10.1016/j.ceca.2007.03.004] [PMID: 17517433] 
[47] 
Kim MS, Zeng W, Yuan JP, Shin DM, Worley PF, Muallem S. Native store-operated Ca2+ influx requires the channel function of Orai1 and TRPC1. J Biol Chem  2009; 284(15): 9733-41.
[http://dx.doi.org/10.1074/jbc.M808097200] [PMID: 19228695] 
[48] 
Jardin I, Lopez JJ, Salido GM, Rosado JA. Orai1 mediates the interaction between STIM1 and hTRPC1 and regulates the mode of activation of hTRPC1-forming Ca2+ channels. J Biol Chem  2008; 283(37): 25296-304.
[http://dx.doi.org/10.1074/jbc.M802904200] [PMID: 18644792] 
[49] 
Ong HL, Cheng KT, Liu X, et al. Dynamic assembly of TRPC1-STIM1-Orai1 ternary complex is involved in store-operated calcium influx. Evidence for similarities in store-operated and calcium release-activated calcium channel components. J Biol Chem  2007; 282(12): 9105-16.
[http://dx.doi.org/10.1074/jbc.M608942200] [PMID: 17224452] 
[50] 
Cioffi DL, Wu S, Chen H, et al. Orai1 determines calcium selectivity of an endogenous TRPC heterotetramer channel. Circ Res  2012; 110(11): 1435-44.
[http://dx.doi.org/10.1161/CIRCRESAHA.112.269506] [PMID: 22534489] 
[51] 
Sundivakkam PC, Freichel M, Singh V, et al. The Ca2+ sensor stromal interaction molecule 1 (STIM1) is necessary and sufficient for the store-operated Ca2+ entry function of transient receptor potential canonical (TRPC) 1 and 4 channels in endothelial cells. Mol Pharmacol  2012; 81(4): 510-26.
[http://dx.doi.org/10.1124/mol.111.074658] [PMID: 22210847] 
[52] 
Sabourin J, Bartoli F, Antigny F, Gomez AM, Benitah JP. Transient receptor potential canonical (TRPC)/orai1-dependent store-operated ca2+ channels: New targets of aldosterone in cardiomyocytes. J Biol Chem  2016; 291(25): 13394-409.
[http://dx.doi.org/10.1074/jbc.M115.693911] [PMID: 27129253] 
[53] 
Hoth M, Fanger CM, Lewis RS. Mitochondrial regulation of store-operated calcium signaling in T lymphocytes. J Cell Biol  1997; 137(3): 633-48.
[http://dx.doi.org/10.1083/jcb.137.3.633] [PMID: 9151670] 
[54] 
Hoth M, Button DC, Lewis RS. Mitochondrial control of calcium-channel gating: A mechanism for sustained signaling and transcriptional activation in T lymphocytes. Proc Natl Acad Sci USA  2000; 97(19): 10607-12.
[http://dx.doi.org/10.1073/pnas.180143997] [PMID: 10973476] 
[55] 
Bezprozvanny I, Watras J, Ehrlich BE. Bell-shaped calcium-response curves of Ins(1,4,5)P3- and calcium-gated channels from endoplasmic reticulum of cerebellum. Nature  1991; 351(6329): 751-4.
[http://dx.doi.org/10.1038/351751a0] [PMID: 1648178] 
[56] 
Glitsch MD, Bakowski D, Parekh AB. Store-operated Ca2+ entry depends on mitochondrial Ca2+ uptake. EMBO J  2002; 21(24): 6744-54.
[http://dx.doi.org/10.1093/emboj/cdf675] [PMID: 12485995] 
[57] 
Gilabert JA, Parekh AB. Respiring mitochondria determine the pattern of activation and inactivation of the store-operated Ca2+ current I(CRAC). EMBO J  2000; 19(23): 6401-7.
[http://dx.doi.org/10.1093/emboj/19.23.6401] [PMID: 11101513] 
[58] 
Gilabert JA, Bakowski D, Parekh AB. Energized mitochondria increase the dynamic range over which inositol 1,4,5-trisphosphate activates store-operated calcium influx. EMBO J  2001; 20(11): 2672-9.
[http://dx.doi.org/10.1093/emboj/20.11.2672] [PMID: 11387202] 
[59] 
Montalvo GB, Artalejo AR, Gilabert JA. ATP from subplasmalemmal mitochondria controls Ca2+-dependent inactivation of CRAC channels. J Biol Chem  2006; 281(47): 35616-23.
[http://dx.doi.org/10.1074/jbc.M603518200] [PMID: 16982621] 
[60] 
Malli R, Frieden M, Trenker M, Graier WF. The role of mitochondria for Ca2+ refilling of the endoplasmic reticulum. J Biol Chem  2005; 280(13): 12114-22.
[http://dx.doi.org/10.1074/jbc.M409353200] [PMID: 15659398] 
[61] 
Naghdi S, Waldeck-Weiermair M, Fertschai I, Poteser M, Graier WF, Malli R. Mitochondrial Ca2+ uptake and not mitochondrial motility is required for STIM1-Orai1-dependent store-operated Ca2+ entry. J Cell Sci  2010; 123(Pt 15): 2553-64.
[http://dx.doi.org/10.1242/jcs.070151] [PMID: 20587595] 
[62] 
Deak AT, Blass S, Khan MJ, et al. IP3-mediated STIM1 oligomerization requires intact mitochondrial Ca2+ uptake. J Cell Sci  2014; 127(Pt 13): 2944-55.
[http://dx.doi.org/10.1242/jcs.149807] [PMID: 24806964] 
[63] 
Pascual-Caro C, Berrocal M, Lopez-Guerrero AM, et al. STIM1 deficiency is linked to Alzheimer’s disease and triggers cell death in SH-SY5Y cells by upregulation of L-type voltage-operated Ca2+ entry. J Mol Med (Berl)  2018; 96(10): 1061-79.
[http://dx.doi.org/10.1007/s00109-018-1677-y] [PMID: 30088035] 
[64] 
Henke N, Albrecht P, Pfeiffer A, Toutzaris D, Zanger K, Methner A. Stromal interaction molecule 1 (STIM1) is involved in the regulation of mitochondrial shape and bioenergetics and plays a role in oxidative stress. J Biol Chem  2012; 287(50): 42042-52.
[http://dx.doi.org/10.1074/jbc.M112.417212] [PMID: 23076152] 
[65] 
Li B, Xiao L, Wang ZY, Zheng PS. Knockdown of STIM1 inhibits 6-hydroxydopamine-induced oxidative stress through attenuating calcium-dependent ER stress and mitochondrial dysfunction in undifferentiated PC12 cells. Free Radic Res  2014; 48(7): 758-68.
[http://dx.doi.org/10.3109/10715762.2014.905687] [PMID: 24720513] 
[66] 
Tu CC, Wan BY, Zeng Y. STIM2 knockdown protects against ischemia/reperfusion injury through reducing mitochondrial calcium overload and preserving mitochondrial function. Life Sci  2020; 247116560
[http://dx.doi.org/10.1016/j.lfs.2019.116560] [PMID: 31200000] 
[67] 
Patel S, Docampo R. Acidic calcium stores open for business: Expanding the potential for intracellular Ca2+ signaling. Trends Cell Biol  2010; 20(5): 277-86.
[http://dx.doi.org/10.1016/j.tcb.2010.02.003] [PMID: 20303271] 
[68] 
Ronco V, Potenza DM, Denti F, et al. A novel Ca2+-mediated cross-talk between endoplasmic reticulum and acidic organelles: Implications for NAADP-dependent Ca2+ signalling. Cell Calcium  2015; 57(2): 89-100.
[http://dx.doi.org/10.1016/j.ceca.2015.01.001] [PMID: 25655285] 
[69] 
Burgoyne T, Patel S, Eden ER. Calcium signaling at ER membrane contact sites. Biochimica Et Biophysica Acta (BBA). Mol Cell Res  2015; 1853(9): 2012-7.
[70] 
Hui L, Geiger NH, Bloor-Young D, Churchill GC, Geiger JD, Chen X. Release of calcium from endolysosomes increases calcium influx through N-type calcium channels: Evidence for acidic store-operated calcium entry in neurons. Cell Calcium  2015; 58(6): 617-27.
[http://dx.doi.org/10.1016/j.ceca.2015.10.001] [PMID: 26475051] 
[71] 
Concepcion AR, Feske S. Regulation of epithelial ion transport in exocrine glands by store-operated Ca2+ entry. Cell Calcium  2017; 63: 53-9.
[http://dx.doi.org/10.1016/j.ceca.2016.12.004] [PMID: 28027799] 
[72] 
Maus M, Cuk M, Patel B, et al. Store-Operated Ca2+ Entry controls induction of lipolysis and the transcriptional reprogramming to lipid metabolism. Cell Metab  2017; 25(3): 698-712.
[http://dx.doi.org/10.1016/j.cmet.2016.12.021] [PMID: 28132808] 
[73] 
Ozcan L, Wong CC, Li G, et al. Calcium signaling through CaMKII regulates hepatic glucose production in fasting and obesity. Cell Metab  2012; 15(5): 739-51.
[http://dx.doi.org/10.1016/j.cmet.2012.03.002] [PMID: 22503562] 
[74] 
Barritt GJ, Chen J, Rychkov GY. Ca2+-permeable channels in the hepatocyte plasma membrane and their roles in hepatocyte physiology. Biochim Biophys Acta  2008; 1783(5): 651-72.
[http://dx.doi.org/10.1016/j.bbamcr.2008.01.016] [PMID: 18291110] 
[75] 
Shaw PJ, Feske S. Regulation of lymphocyte function by ORAI and STIM proteins in infection and autoimmunity. J Physiol  2012; 590(17): 4157-67.
[http://dx.doi.org/10.1113/jphysiol.2012.233221] [PMID: 22615435] 
[76] 
Michaelsen K, Lohmann C. Calcium dynamics at developing synapses: Mechanisms and functions. Eur J Neurosci  2010; 32(2): 218-23.
[http://dx.doi.org/10.1111/j.1460-9568.2010.07341.x] [PMID: 20646046] 
[77] 
Berridge MJ. Neuronal calcium signaling. Neuron  1998; 21(1): 13-26.
[http://dx.doi.org/10.1016/S0896-6273(00)80510-3] [PMID: 9697848] 
[78] 
Lohmann C, Wong RO. Regulation of dendritic growth and plasticity by local and global calcium dynamics. Cell Calcium  2005; 37(5): 403-9.
[http://dx.doi.org/10.1016/j.ceca.2005.01.008] [PMID: 15820387] 
[79] 
Tang Y, Zucker RS. Mitochondrial involvement in post-tetanic potentiation of synaptic transmission. Neuron  1997; 18(3): 483-91.
[http://dx.doi.org/10.1016/S0896-6273(00)81248-9] [PMID: 9115741] 
[80] 
Tanaka D, Nakada K, Takao K, et al. Normal mitochondrial respiratory function is essential for spatial remote memory in mice. Mol Brain  2008; 1: 21-1.
[http://dx.doi.org/10.1186/1756-6606-1-21] [PMID: 19087269] 
[81] 
Berna-Erro A, Braun A, Kraft R, et al. STIM2 regulates capacitive Ca2+ entry in neurons and plays a key role in hypoxic neuronal cell death. Sci Signal  2009; 2(93): ra67-7.
[http://dx.doi.org/10.1126/scisignal.2000522] [PMID: 19843959] 
[82] 
Sun S, Zhang H, Liu J, et al. Reduced synaptic STIM2 expression and impaired store-operated calcium entry cause destabilization of mature spines in mutant presenilin mice. Neuron  2014; 82(1): 79-93.
[http://dx.doi.org/10.1016/j.neuron.2014.02.019] [PMID: 24698269] 
[83] 
Samtleben S, Wachter B, Blum R. Store-operated calcium entry compensates fast ER calcium loss in resting hippocampal neurons. Cell Calcium  2015; 58(2): 147-59.
[http://dx.doi.org/10.1016/j.ceca.2015.04.002] [PMID: 25957620] 
[84] 
Majewski L, Kuznicki J. SOCE in neurons: Signaling or just refilling? Biochimica et Biophysica Acta (BBA) -. Mol Cell Res  2015; 1853(9): 1940-52.
[85] 
Müller MS, Fox R, Schousboe A, Waagepetersen HS, Bak LK. Astrocyte glycogenolysis is triggered by store-operated calcium entry and provides metabolic energy for cellular calcium homeostasis. Glia  2014; 62(4): 526-34.
[http://dx.doi.org/10.1002/glia.22623] [PMID: 24464850] 
[86] 
The Human Protein Atlas. 2020.
[87] 
Uhlén M, Fagerberg L, Hallström BM, et al. Proteomics. Tissue-based map of the human proteome. Science  2015; 347(6220)1260419
[http://dx.doi.org/10.1126/science.1260419] [PMID: 25613900] 
[88] 
Baba A, Yasui T, Fujisawa S, et al. Activity-evoked capacitative Ca2+ entry: Implications in synaptic plasticity. J Neurosci  2003; 23(21): 7737-41.
[http://dx.doi.org/10.1523/JNEUROSCI.23-21-07737.2003] [PMID: 12944501] 
[89] 
Emptage NJ, Reid CA, Fine A. Calcium stores in hippocampal synaptic boutons mediate short-term plasticity, store-operated Ca2+ entry, and spontaneous transmitter release. Neuron  2001; 29(1): 197-208.
[http://dx.doi.org/10.1016/S0896-6273(01)00190-8] [PMID: 11182091] 
[90] 
Narayanan R, Dougherty KJ, Johnston D. Calcium store depletion induces persistent perisomatic increases in the functional density of h channels in hippocampal pyramidal neurons. Neuron  2010; 68(5): 921-35.
[http://dx.doi.org/10.1016/j.neuron.2010.11.033] [PMID: 21145005] 
[91] 
Ferraguti F, Shigemoto R. Metabotropic glutamate receptors. Cell Tissue Res  2006; 326(2): 483-504.
[http://dx.doi.org/10.1007/s00441-006-0266-5] [PMID: 16847639] 
[92] 
Raymond CR, Thompson VL, Tate WP, Abraham WC. Metabotropic glutamate receptors trigger homosynaptic protein synthesis to prolong long-term potentiation. J Neurosci  2000; 20(3): 969-76.
[http://dx.doi.org/10.1523/JNEUROSCI.20-03-00969.2000] [PMID: 10648701] 
[93] 
Miura M, Watanabe M, Offermanns S, Simon MI, Kano M. Group I metabotropic glutamate receptor signaling via Galpha q/Galpha 11 secures the induction of long-term potentiation in the hippocampal area CA1. J Neurosci  2002; 22(19): 8379-90.
[http://dx.doi.org/10.1523/JNEUROSCI.22-19-08379.2002] [PMID: 12351712] 
[94] 
Youn DH. Differential roles of signal transduction mechanisms in long-term potentiation of excitatory synaptic transmission induced by activation of group I mGluRs in the spinal trigeminal subnucleus oralis. Brain Res Bull  2014; 108: 37-43.
[http://dx.doi.org/10.1016/j.brainresbull.2014.08.003] [PMID: 25149878] 
[95] 
Shigemoto R, Abe T, Nomura S, Nakanishi S, Hirano T. Antibodies inactivating mGluR1 metabotropic glutamate receptor block long-term depression in cultured Purkinje cells. Neuron  1994; 12(6): 1245-55.
[http://dx.doi.org/10.1016/0896-6273(94)90441-3] [PMID: 7912091] 
[96] 
Grueter BA, Gosnell HB, Olsen CM, et al. Extracellular-signal regulated kinase 1-dependent metabotropic glutamate receptor 5-induced long-term depression in the bed nucleus of the stria terminalis is disrupted by cocaine administration. J Neurosci  2006; 26(12): 3210-9.
[http://dx.doi.org/10.1523/JNEUROSCI.0170-06.2006] [PMID: 16554472] 
[97] 
Aiba A, Chen C, Herrup K, Rosenmund C, Stevens CF, Tonegawa S. Reduced hippocampal long-term potentiation and context-specific deficit in associative learning in mGluR1 mutant mice. Cell  1994; 79(2): 365-75.
[http://dx.doi.org/10.1016/0092-8674(94)90204-6] [PMID: 7954802] 
[98] 
González-Sánchez P, Del Arco A, Esteban JA, Satrústegui J. Store-operated calcium entry is required for mGluR-dependent long term depression in cortical neurons. Front Cell Neurosci  2017; 11: 363.
[http://dx.doi.org/10.3389/fncel.2017.00363] [PMID: 29311823] 
[99] 
Ramos B, Gaudillière B, Bonni A, Gill G. Transcription factor Sp4 regulates dendritic patterning during cerebellar maturation. Proc Natl Acad Sci USA  2007; 104(23): 9882-7.
[http://dx.doi.org/10.1073/pnas.0701946104] [PMID: 17535924] 
[100] 
Ramos B, Valín A, Sun X, Gill G. Sp4-dependent repression of neurotrophin-3 limits dendritic branching. Mol Cell Neurosci  2009; 42(2): 152-9.
[http://dx.doi.org/10.1016/j.mcn.2009.06.008] [PMID: 19555762] 
[101] 
Vandesompele J, De Peter K, Pattyn F, et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes Genome biology  2002; 3(7)RESEARCH0034
[102] 
Lalonde J, Saia G, Gill G. Store-operated calcium entry promotes the degradation of the transcription factor Sp4 in resting neurons. Sci Signal  2014; 7(328): ra51.
[http://dx.doi.org/10.1126/scisignal.2005242] [PMID: 24894994] 
[103] 
Garcia-Alvarez G, Shetty MS, Lu B, et al. Impaired spatial memory and enhanced long-term potentiation in mice with forebrain-specific ablation of the Stim genes. Front Behav Neurosci  2015; 9(180): 180.
[http://dx.doi.org/10.3389/fnbeh.2015.00180] [PMID: 26236206] 
[104] 
Hartmann J, Karl RM, Alexander RP, et al. STIM1 controls neuronal Ca2+ signaling, mGluR1-dependent synaptic transmission, and cerebellar motor behavior. Neuron  2014; 82(3): 635-44.
[http://dx.doi.org/10.1016/j.neuron.2014.03.027] [PMID: 24811382] 
[105] 
Yap KAF, Shetty MS, Garcia-Alvarez G, et al. STIM2 regulates AMPA receptor trafficking and plasticity at hippocampal synapses. Neurobiol Learn Mem  2017; 138: 54-61.
[http://dx.doi.org/10.1016/j.nlm.2016.08.007] [PMID: 27544849] 
[106] 
Garcia-Alvarez G, Lu B, Yap KA, et al. STIM2 regulates PKA-dependent phosphorylation and trafficking of AMPARs. Mol Biol Cell  2015; 26(6): 1141-59.
[http://dx.doi.org/10.1091/mbc.E14-07-1222] [PMID: 25609091] 
[107] 
Korkotian E, Oni-Biton E, Segal M. The role of the store-operated calcium entry channel Orai1 in cultured rat hippocampal synapse formation and plasticity. J Physiol  2017; 595(1): 125-40.
[http://dx.doi.org/10.1113/JP272645] [PMID: 27393042] 
[108] 
Kim SJ, Kim YS, Yuan JP, Petralia RS, Worley PF, Linden DJ. Activation of the TRPC1 cation channel by metabotropic glutamate receptor mGluR1. Nature  2003; 426(6964): 285-91.
[http://dx.doi.org/10.1038/nature02162] [PMID: 14614461] 
[109] 
Hartmann J, Dragicevic E, Adelsberger H, et al. TRPC3 channels are required for synaptic transmission and motor coordination. Neuron  2008; 59(3): 392-8.
[http://dx.doi.org/10.1016/j.neuron.2008.06.009] [PMID: 18701065] 
[110] 
Amaral MD, Pozzo-Miller L. TRPC3 channels are necessary for brain-derived neurotrophic factor to activate a nonselective cationic current and to induce dendritic spine formation. J Neurosci  2007; 27(19): 5179-89.
[http://dx.doi.org/10.1523/JNEUROSCI.5499-06.2007] [PMID: 17494704] 
[111] 
Neuner SM, Wilmott LA, Hope KA, et al. TRPC3 channels critically regulate hippocampal excitability and contextual fear memory. Behav Brain Res  2015; 281: 69-77.
[http://dx.doi.org/10.1016/j.bbr.2014.12.018] [PMID: 25513972] 
[112] 
Zhou J, Du W, Zhou K, et al. Critical role of TRPC6 channels in the formation of excitatory synapses. Nat Neurosci  2008; 11(7): 741-3.
[http://dx.doi.org/10.1038/nn.2127] [PMID: 18516035] 
[113] 
Wang J, Lu R, Yang J, et al. TRPC6 specifically interacts with APP to inhibit its cleavage by γ-secretase and reduce Aβ production. Nat Commun  2015; 6(1): 8876.
[http://dx.doi.org/10.1038/ncomms9876] [PMID: 26581893] 
[114] 
Zhang H, Wu L, Pchitskaya E, et al. Neuronal store-operated calcium entry and mushroom spine loss in amyloid precursor protein knock-in mouse model of Alzheimer’s disease. J Neurosci  2015; 35(39): 13275-86.
[http://dx.doi.org/10.1523/JNEUROSCI.1034-15.2015] [PMID: 26424877] 
[115] 
Nicholls DG, Budd SL. Mitochondria and neuronal survival. Physiol Rev  2000; 80(1): 315-60.
[http://dx.doi.org/10.1152/physrev.2000.80.1.315] [PMID: 10617771] 
[116] 
Mattson MP, Gleichmann M, Cheng A. Mitochondria in neuroplasticity and neurological disorders. Neuron  2008; 60(5): 748-66.
[http://dx.doi.org/10.1016/j.neuron.2008.10.010] [PMID: 19081372] 
[117] 
Vos M, Lauwers E, Verstreken P. Synaptic mitochondria in synaptic transmission and organization of vesicle pools in health and disease. Front Synaptic Neurosci  2010; 2: 139-9.
[http://dx.doi.org/10.3389/fnsyn.2010.00139] [PMID: 21423525] 
[118] 
Marland JRK, Hasel P, Bonnycastle K, Cousin MA. Mitochondrial calcium uptake modulates synaptic vesicle endocytosis in central nerve terminals. J Biol Chem  2016; 291(5): 2080-6.
[http://dx.doi.org/10.1074/jbc.M115.686956] [PMID: 26644474] 
[119] 
Billups B, Forsythe ID. Presynaptic mitochondrial calcium sequestration influences transmission at mammalian central synapses. J Neurosci  2002; 22(14): 5840-7.
[http://dx.doi.org/10.1523/JNEUROSCI.22-14-05840.2002] [PMID: 12122046] 
[120] 
Marchant JS, Patel S. Two-pore channels at the intersection of endolysosomal membrane traffic. Portland Press Ltd. 2015.
[http://dx.doi.org/10.1042/BST20140303] 
[121] 
Davis LC, Morgan AJ, Galione A. NAADP-regulated two-pore channels drive phagocytosis through endo-lysosomal Ca2+ nanodomains, calcineurin and dynamin. EMBO J  2020; 39(14)e104058
[http://dx.doi.org/10.15252/embj.2019104058] [PMID: 32510172] 
[122] 
Rosato AS, Montefusco S, Soldati C, et al. TRPML1 links lysosomal calcium to autophagosome biogenesis through the activation of the CaMKKβ/VPS34 pathway. Nat Commun  2019; 10(1): 1-16.
[PMID: 30602773] 
[123] 
Padamsey Z, McGuinness L, Bardo SJ, et al. Activity-dependent exocytosis of lysosomes regulates the structural plasticity of dendritic spines. Neuron  2017; 93(1): 132-46.
[http://dx.doi.org/10.1016/j.neuron.2016.11.013] [PMID: 27989455] 
[124] 
Foster WJ, Taylor HBC, Padamsey Z, Jeans AF, Galione A, Emptage NJ. Hippocampal mGluR1-dependent long-term potentiation requires NAADP-mediated acidic store Ca2+ signaling. Sci Signal  2018; 11(558)eaat9093
[http://dx.doi.org/10.1126/scisignal.aat9093] [PMID: 30482851] 
[125] 
Celsi F, Pizzo P, Brini M, et al. Mitochondria, calcium and cell death: A deadly triad in neurodegeneration. Biochim Biophys Acta  2009; 1787(5): 335-44.
[http://dx.doi.org/10.1016/j.bbabio.2009.02.021] [PMID: 19268425] 
[126] 
Bezprozvanny I. Calcium signaling and neurodegenerative diseases. Trends Mol Med  2009; 15(3): 89-100.
[http://dx.doi.org/10.1016/j.molmed.2009.01.001] [PMID: 19230774] 
[127] 
Petryniak MA, Wurtman RJ, Slack BE. Elevated intracellular calcium concentration increases secretory processing of the amyloid precursor protein by a tyrosine phosphorylation-dependent mechanism. Biochem J  1996; 320(Pt 3): 957-63.
[http://dx.doi.org/10.1042/bj3200957] [PMID: 9003386] 
[128] 
Etcheberrigaray R, Hirashima N, Nee L, et al. Calcium responses in fibroblasts from asymptomatic members of Alzheimer’s disease families. Neurobiol Dis  1998; 5(1): 37-45.
[http://dx.doi.org/10.1006/nbdi.1998.0176] [PMID: 9702786] 
[129] 
Yoo AS, Cheng I, Chung S, et al. Presenilin-mediated modulation of capacitative calcium entry. Neuron  2000; 27(3): 561-72.
[http://dx.doi.org/10.1016/S0896-6273(00)00066-0] [PMID: 11055438] 
[130] 
Cheung K-H, Shineman D, Müller M, et al. Mechanism of Ca2+ disruption in Alzheimer’s disease by presenilin regulation of InsP3 receptor channel gating. Neuron  2008; 58(6): 871-83.
[http://dx.doi.org/10.1016/j.neuron.2008.04.015] [PMID: 18579078] 
[131] 
Giacomello M, Barbiero L, Zatti G, et al. Reduction of Ca2+ stores and capacitative Ca2+ entry is associated with the familial Alzheimer’s disease presenilin-2 T122R mutation and anticipates the onset of dementia. Neurobiol Dis  2005; 18(3): 638-48.
[http://dx.doi.org/10.1016/j.nbd.2004.10.016] [PMID: 15755689] 
[132] 
Lessard CB, Lussier MP, Cayouette S, Bourque G, Boulay G. The overexpression of presenilin2 and Alzheimer’s-disease-linked presenilin2 variants influences TRPC6-enhanced Ca2+ entry into HEK293 cells. Cell Signal  2005; 17(4): 437-45.
[http://dx.doi.org/10.1016/j.cellsig.2004.09.005] [PMID: 15601622] 
[133] 
Stutzmann GE, Smith I, Caccamo A, Oddo S, Laferla FM, Parker I. Enhanced ryanodine receptor recruitment contributes to Ca2+ disruptions in young, adult, and aged Alzheimer’s disease mice. J Neurosci  2006; 26(19): 5180-9.
[http://dx.doi.org/10.1523/JNEUROSCI.0739-06.2006] [PMID: 16687509] 
[134] 
Hayrapetyan V, Rybalchenko V, Rybalchenko N, Koulen P. The N-terminus of presenilin-2 increases single channel activity of brain ryanodine receptors through direct protein-protein interaction. Cell Calcium  2008; 44(5): 507-18.
[http://dx.doi.org/10.1016/j.ceca.2008.03.004] [PMID: 18440065] 
[135] 
Popugaeva E, Bezprozvanny I. Role of endoplasmic reticulum Ca2+ signaling in the pathogenesis of Alzheimer disease. Front Mol Neurosci  2013; 6: 29.
[http://dx.doi.org/10.3389/fnmol.2013.00029] [PMID: 24065882] 
[136] 
Thibault O, Gant JC, Landfield PW. Expansion of the calcium hypothesis of brain aging and Alzheimer’s disease: Minding the store. Aging Cell  2007; 6(3): 307-17.
[http://dx.doi.org/10.1111/j.1474-9726.2007.00295.x] [PMID: 17465978] 
[137] 
Del Prete D, Checler F, Chami M. Ryanodine receptors: Physiological function and deregulation in Alzheimer disease. Mol Neurodegener  2014; 9: 21-1.
[http://dx.doi.org/10.1186/1750-1326-9-21] [PMID: 24902695] 
[138] 
Scheuner D, Eckman C, Jensen M, et al. Secreted amyloid β-protein similar to that in the senile plaques of Alzheimer’s disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer’s disease. Nat Med  1996; 2(8): 864-70.
[http://dx.doi.org/10.1038/nm0896-864] [PMID: 8705854] 
[139] 
Green KN, Demuro A, Akbari Y, et al. SERCA pump activity is physiologically regulated by presenilin and regulates amyloid β production. J Cell Biol  2008; 181(7): 1107-16.
[http://dx.doi.org/10.1083/jcb.200706171] [PMID: 18591429] 
[140] 
Mattson MP. ER calcium and Alzheimer’s disease: In a state of flux. Sci Signal  2010; 3(114): pe10-0.
[http://dx.doi.org/10.1126/scisignal.3114pe10] [PMID: 20332425] 
[141] 
Cheung K-H, Mei L, Mak DO, et al. Gain-of-function enhancement of IP3 receptor modal gating by familial Alzheimer’s disease-linked presenilin mutants in human cells and mouse neurons. Sci Signal  2010; 3(114): ra22-.
[http://dx.doi.org/10.1126/scisignal.2000818] [PMID: 20332427] 
[142] 
Leissring MA, Akbari Y, Fanger CM, Cahalan MD, Mattson MP, LaFerla FM. Capacitative calcium entry deficits and elevated luminal calcium content in mutant presenilin-1 knockin mice. J Cell Biol  2000; 149(4): 793-8.
[http://dx.doi.org/10.1083/jcb.149.4.793] [PMID: 10811821] 
[143] 
Secondo A, Bagetta G, Amantea D. On the role of store-operated calcium entry in acute and chronic neurodegenerative diseases. Front Mol Neurosci  2018; 11: 87-7.
[http://dx.doi.org/10.3389/fnmol.2018.00087] [PMID: 29623030] 
[144] 
Peterson C, Gibson GE, Blass JP. Altered calcium uptake in cultured skin fibroblasts from patients with Alzheimer’s disease. N Engl J Med  1985; 312(16): 1063-5.
[http://dx.doi.org/10.1056/NEJM198504183121618] [PMID: 3982463] 
[145] 
Ito E, Oka K, Etcheberrigaray R, et al. Internal Ca2+ mobilization is altered in fibroblasts from patients with Alzheimer disease. Proc Natl Acad Sci USA  1994; 91(2): 534-8.
[http://dx.doi.org/10.1073/pnas.91.2.534] [PMID: 8290560] 
[146] 
Mattson MP, Chan SL. Dysregulation of cellular calcium homeostasis in Alzheimer’s disease: Bad genes and bad habits. J Mol Neurosci  2001; 17(2): 205-24.
[http://dx.doi.org/10.1385/JMN:17:2:205] [PMID: 11816794] 
[147] 
Guo Q, Furukawa K, Sopher BL, et al. Alzheimer’s PS-1 mutation perturbs calcium homeostasis and sensitizes PC12 cells to death induced by amyloid beta-peptide. Neuroreport  1996; 8(1): 379-83.
[http://dx.doi.org/10.1097/00001756-199612200-00074] [PMID: 9051814] 
[148] 
Leissring MA, Parker I, LaFerla FM. Presenilin-2 mutations modulate amplitude and kinetics of inositol 1, 4,5-trisphosphate-mediated calcium signals. J Biol Chem  1999; 274(46): 32535-8.
[http://dx.doi.org/10.1074/jbc.274.46.32535] [PMID: 10551803] 
[149] 
Herms J, Schneider I, Dewachter I, Caluwaerts N, Kretzschmar H, Van Leuven F. Capacitive calcium entry is directly attenuated by mutant presenilin-1, independent of the expression of the amyloid precursor protein. J Biol Chem  2003; 278(4): 2484-9.
[http://dx.doi.org/10.1074/jbc.M206769200] [PMID: 12431992] 
[150] 
Bojarski L, Pomorski P, Szybinska A, et al. Presenilin-dependent expression of STIM proteins and dysregulation of capacitative Ca2+ entry in familial Alzheimer’s disease. Biochim Biophys Acta  2009; 1793(6): 1050-7.
[http://dx.doi.org/10.1016/j.bbamcr.2008.11.008] [PMID: 19111578] 
[151] 
Tong BC-K, Lee CS, Cheng WH, Lai KO, Foskett JK, Cheung KH. Familial Alzheimer’s disease-associated presenilin 1 mutants promote γ-secretase cleavage of STIM1 to impair store-operated Ca2+ entry. Sci Signal  2016; 9(444): ra89-9.
[http://dx.doi.org/10.1126/scisignal.aaf1371] [PMID: 27601731] 
[152] 
Greotti E, Capitanio P, Wong A, Pozzan T, Pizzo P, Pendin D. Familial Alzheimer’s disease-linked presenilin mutants and intracellular Ca2+ handling: A single-organelle, FRET-based analysis. Cell Calcium  2019; 79: 44-56.
[http://dx.doi.org/10.1016/j.ceca.2019.02.005] [PMID: 30822648] 
[153] 
Zeiger W, Vetrivel KS, Buggia-Prévot V, et al. Ca2+ influx through store-operated Ca2+ channels reduces Alzheimer disease β-amyloid peptide secretion. J Biol Chem  2013; 288(37): 26955-66.
[http://dx.doi.org/10.1074/jbc.M113.473355] [PMID: 23902769] 
[154] 
Lüscher C, Malenka RC. NMDA receptor-dependent long-term potentiation and long-term depression (LTP/LTD). Cold Spring Harb Perspect Biol  2012; 4(6)a005710
[http://dx.doi.org/10.1101/cshperspect.a005710] [PMID: 22510460] 
[155] 
Zhang H, Sun S, Wu L, et al. Store-operated calcium channel complex in postsynaptic spines: A new therapeutic target for Alzheimer’s disease treatment. J Neurosci  2016; 36(47): 11837-50.
[http://dx.doi.org/10.1523/JNEUROSCI.1188-16.2016] [PMID: 27881772] 
[156] 
Swerdlow RH, Khan SMA. “mitochondrial cascade hypothesis” for sporadic Alzheimer’s disease. Med Hypotheses  2004; 63(1): 8-20.
[http://dx.doi.org/10.1016/j.mehy.2003.12.045] [PMID: 15193340] 
[157] 
Reddy PH, Beal MF. Are mitochondria critical in the pathogenesis of Alzheimer’s disease? Brain Res Brain Res Rev  2005; 49(3): 618-32.
[http://dx.doi.org/10.1016/j.brainresrev.2005.03.004] [PMID: 16269322] 
[158] 
Lin MT, Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature  2006; 443(7113): 787-95.
[http://dx.doi.org/10.1038/nature05292] [PMID: 17051205] 
[159] 
Parihar MS, Brewer GJ. Mitoenergetic failure in Alzheimer disease. Am J Physiol Cell Physiol  2007; 292(1): C8-C23.
[http://dx.doi.org/10.1152/ajpcell.00232.2006] [PMID: 16807300] 
[160] 
Jadiya P, Kolmetzky DW, Tomar D, et al. Impaired mitochondrial calcium efflux contributes to disease progression in models of Alzheimer’s disease. Nat Commun  2019; 10(1): 3885.
[http://dx.doi.org/10.1038/s41467-019-11813-6] [PMID: 31467276] 
[161] 
Hedskog L, Pinho CM, Filadi R, et al. Modulation of the endoplasmic reticulum-mitochondria interface in Alzheimer’s disease and related models. Proc Natl Acad Sci USA  2013; 110(19): 7916-21.
[http://dx.doi.org/10.1073/pnas.1300677110] [PMID: 23620518] 
[162] 
Area-Gomez E, de Groof A, Bonilla E, et al. A key role for MAM in mediating mitochondrial dysfunction in Alzheimer disease. Cell Death Dis  2018; 9(3): 335.
[http://dx.doi.org/10.1038/s41419-017-0215-0] [PMID: 29491396] 
[163] 
Toglia P, Cheung KH, Mak DO, Ullah G. Impaired mitochondrial function due to familial Alzheimer’s disease-causing presenilins mutants via Ca(2+) disruptions. Cell Calcium  2016; 59(5): 240-50.
[http://dx.doi.org/10.1016/j.ceca.2016.02.013] [PMID: 26971122] 
[164] 
Ferreiro E, Oliveira CR, Pereira CMF. The release of calcium from the endoplasmic reticulum induced by amyloid-beta and prion peptides activates the mitochondrial apoptotic pathway. Neurobiol Dis  2008; 30(3): 331-42.
[http://dx.doi.org/10.1016/j.nbd.2008.02.003] [PMID: 18420416] 
[165] 
Sanz-Blasco S, Valero RA, Rodríguez-Crespo I, Villalobos C, Núñez L. Mitochondrial Ca2+ overload underlies Abeta oligomers neurotoxicity providing an unexpected mechanism of neuroprotection by NSAIDs. PLoS One  2008; 3(7): e2718-8.
[http://dx.doi.org/10.1371/journal.pone.0002718] [PMID: 18648507] 
[166] 
Du H, Guo L, Zhang W, Rydzewska M, Yan S. Cyclophilin D deficiency improves mitochondrial function and learning/memory in aging Alzheimer disease mouse model. Neurobiol Aging  2011; 32(3): 398-406.
[http://dx.doi.org/10.1016/j.neurobiolaging.2009.03.003] [PMID: 19362755] 
[167] 
Park I, Londhe AM, Lim JW, et al. Discovery of non-peptidic small molecule inhibitors of cyclophilin D as neuroprotective agents in Aβ-induced mitochondrial dysfunction. J Comput Aided Mol Des  2017; 31(10): 929-41.
[http://dx.doi.org/10.1007/s10822-017-0067-9] [PMID: 28913661] 
[168] 
Du H, Guo L, Fang F, et al. Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer’s disease. Nat Med  2008; 14(10): 1097-105.
[http://dx.doi.org/10.1038/nm.1868] [PMID: 18806802] 
[169] 
Ma T, Gong K, Yan Y, Song B, Zhang X, Gong Y. Mitochondrial modulation of store-operated Ca2+ entry in model cells of Alzheimer’s disease. Biochem Biophys Res Commun  2012; 426(2): 196-202.
[http://dx.doi.org/10.1016/j.bbrc.2012.08.062] [PMID: 22935417] 
[170] 
Coffey EE, Beckel JM, Laties AM, Mitchell CH. Lysosomal alkalization and dysfunction in human fibroblasts with the Alzheimer’s disease-linked presenilin 1 A246E mutation can be reversed with cAMP. Neuroscience  2014; 263: 111-24.
[http://dx.doi.org/10.1016/j.neuroscience.2014.01.001] [PMID: 24418614] 
[171] 
van Weering JRT, Scheper W. Endolysosome and autolysosome dysfunction in Alzheimer’s disease: Where intracellular and extracellular meet. CNS Drugs  2019; 33(7): 639-48.
[http://dx.doi.org/10.1007/s40263-019-00643-1] [PMID: 31165364] 
[172] 
Lee J-H, Yu WH, Kumar A, et al. Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations. Cell  2010; 141(7): 1146-58.
[http://dx.doi.org/10.1016/j.cell.2010.05.008] [PMID: 20541250] 
[173] 
Nixon RA, Cataldo AM, Mathews PM. The endosomal-lysosomal system of neurons in Alzheimer’s disease pathogenesis: A review. Neurochem Res  2000; 25(9-10): 1161-72.
[http://dx.doi.org/10.1023/A:1007675508413] [PMID: 11059790] 
[174] 
Lakpa KL, et al. Readily releasable stores of calcium in neuronal endolysosomes: Physiological and pathophysiological relevance Calcium Signaling.  Springer 2020; pp. 681-97.
[http://dx.doi.org/10.1007/978-3-030-12457-1_27] 
[175] 
Bojarski L, Herms J, Kuznicki J. Calcium dysregulation in Alzheimer’s disease. Neurochem Int  2008; 52(4-5): 621-33.
[http://dx.doi.org/10.1016/j.neuint.2007.10.002] [PMID: 18035450] 
[176] 
Bird GS. Pharmacology of store-operated calcium entry channels.Calcium entry channels in non-excitable cells, PJJ Kozak JA, Editor CRC Press/Taylor & Francis.  2018.
[177] 
Kudo T, Okumura M, Imaizumi K, et al. Altered localization of amyloid precursor protein under endoplasmic reticulum stress. Biochem Biophys Res Commun  2006; 344(2): 525-30.
[http://dx.doi.org/10.1016/j.bbrc.2006.03.173] [PMID: 16630560] 
[178] 
Reyes M, Stanton PK. Induction of hippocampal long-term depression requires release of Ca2+ from separate presynaptic and postsynaptic intracellular stores. J Neurosci  1996; 16(19): 5951-60.
[http://dx.doi.org/10.1523/JNEUROSCI.16-19-05951.1996] [PMID: 8815877] 
[179] 
Bahia PK, Pugh V, Hoyland K, Hensley V, Rattray M, Williams RJ. Neuroprotective effects of phenolic antioxidant tBHQ associate with inhibition of FoxO3a nuclear translocation and activity. J Neurochem  2012; 123(1): 182-91.
[http://dx.doi.org/10.1111/j.1471-4159.2012.07877.x] [PMID: 22804756] 
[180] 
Sennvik K, Benedikz E, Fastbom J, Sundström E, Winblad B, Ankarcrona M. Calcium ionophore A23187 specifically decreases the secretion of beta-secretase cleaved amyloid precursor protein during apoptosis in primary rat cortical cultures. J Neurosci Res  2001; 63(5): 429-37.
[http://dx.doi.org/10.1002/1097-4547(20010301)63:5<429:AID-JNR1038>3.0.CO;2-U] [PMID: 11223918] 
[181] 
Collatz MB, Rüdel R, Brinkmeier H. Intracellular calcium chelator BAPTA protects cells against toxic calcium overload but also alters physiological calcium responses. Cell Calcium  1997; 21(6): 453-9.
[http://dx.doi.org/10.1016/S0143-4160(97)90056-7] [PMID: 9223681] 
[182] 
Putney JW. Pharmacology of store-operated calcium channels. Mol Interv  2010; 10(4): 209-18.
[http://dx.doi.org/10.1124/mi.10.4.4] [PMID: 20729487] 
[183] 
Zhou Y. Mechanism of activation of store-operated calcium entry by 2-aminoethoxydiphenyl borate. Biophysical J  2014; 106(2): 315.
[184] 
Peppiatt CM, Collins TJ, Mackenzie L, et al. 2-Aminoethoxydiphenyl borate (2-APB) antagonises inositol 1,4,5-trisphosphate-induced calcium release, inhibits calcium pumps and has a use-dependent and slowly reversible action on store-operated calcium entry channels. Cell Calcium  2003; 34(1): 97-108.
[http://dx.doi.org/10.1016/S0143-4160(03)00026-5] [PMID: 12767897] 
[185] 
Colton CK, Zhu MX. 2-Aminoethoxydiphenyl borate as a common activator of TRPV1, TRPV2, and TRPV3 channels. Handb Exp Pharmacol  2007; (179): 173-87.
[http://dx.doi.org/10.1007/978-3-540-34891-7_10] [PMID: 17217057] 
[186] 
Hagenston AM, Rudnick ND, Boone CE, Yeckel MF. 2-Aminoethoxydiphenyl-borate (2-APB) increases excitability in pyramidal neurons. Cell Calcium  2009; 45(3): 310-7.
[http://dx.doi.org/10.1016/j.ceca.2008.11.003] [PMID: 19100621] 
[187] 
Lis A, Peinelt C, Beck A, et al. CRACM1, CRACM2, and CRACM3 are store-operated Ca2+ channels with distinct functional properties. Curr Biol  2007; 17(9): 794-800.
[http://dx.doi.org/10.1016/j.cub.2007.03.065] [PMID: 17442569] 
[188] 
Goto J, Suzuki AZ, Ozaki S, et al. Two novel 2-aminoethyl diphenylborinate (2-APB) analogues differentially activate and inhibit store-operated Ca2+ entry via STIM proteins. Cell Calcium  2010; 47(1): 1-10.
[http://dx.doi.org/10.1016/j.ceca.2009.10.004] [PMID: 19945161] 
[189] 
Leuner K, Kazanski V, Müller M, et al. Hyperforin--a key constituent of St. John’s wort specifically activates TRPC6 channels. FASEB J  2007; 21(14): 4101-11.
[http://dx.doi.org/10.1096/fj.07-8110com] [PMID: 17666455] 
[190] 
Montecinos-Oliva C, Schüller A, Inestrosa NC. Tetrahydrohyperforin: a neuroprotective modified natural compound against Alzheimer’s disease. Neural Regen Res  2015; 10(4): 552-4.
[http://dx.doi.org/10.4103/1673-5374.155420] [PMID: 26170810] 
[191] 
Inestrosa NC, Tapia-Rojas C, Griffith TN, et al. Tetrahydrohyperforin prevents cognitive deficit, Aβ deposition, tau phosphorylation and synaptotoxicity in the APPswe/PSEN1ΔE9 model of Alzheimer’s disease: A possible effect on APP processing. Transl Psychiatry  2011; 1(7): e20-0.
[http://dx.doi.org/10.1038/tp.2011.19] [PMID: 22832522] 
[192] 
Abbott AC, Calderon Toledo C, Aranguiz FC, Inestrosa NC, Varela-Nallar L. Tetrahydrohyperforin increases adult hippocampal neurogenesis in wild-type and APPswe/PS1ΔE9 mice. J Alzheimers Dis  2013; 34(4): 873-85.
[http://dx.doi.org/10.3233/JAD-121714] [PMID: 23302657] 
[193] 
Montecinos-Oliva C, Schuller A, Parodi J, Melo F, Inestrosa NC. Effects of tetrahydrohyperforin in mouse hippocampal slices: Neuroprotection, long-term potentiation and TRPC channels. Curr Med Chem  2014; 21(30): 3494-506.
[http://dx.doi.org/10.2174/0929867321666140716091229] [PMID: 25039785] 
[194] 
Cavieres VA, González A, Muñoz VC, et al. Tetrahydrohyperforin inhibits the proteolytic processing of amyloid precursor protein and enhances its degradation by Atg5-dependent autophagy. PLoS One  2015; 10(8)e0136313
[http://dx.doi.org/10.1371/journal.pone.0136313] [PMID: 26308941] 
[195] 
Blanchard AP, Guillemette G, Boulay G. Memantine potentiates agonist-induced Ca2+ responses in HEK 293 cells. Cell Physiol Biochem  2008; 22(1-4): 205-14.
[http://dx.doi.org/10.1159/000149798] [PMID: 18769047] 
[196] 
Gruszczynska-Biegala J, Strucinska K, Maciag F, Majewski L, Sladowska M, Kuznicki J. STIM Protein-NMDA2 receptor interaction decreases NMDA-dependent calcium levels in cortical neurons. Cells  2020; 9(1): 160.
[http://dx.doi.org/10.3390/cells9010160] [PMID: 31936514] 
[197] 
Eskelinen MH, Ngandu T, Tuomilehto J, Soininen H, Kivipelto M. Midlife coffee and tea drinking and the risk of late-life dementia: A population-based CAIDE study. J Alzheimers Dis  2009; 16(1): 85-91.
[http://dx.doi.org/10.3233/JAD-2009-0920] [PMID: 19158424] 
[198] 
Kim Y-S, Kwak SM, Myung S-K. Caffeine intake from coffee or tea and cognitive disorders: A meta-analysis of observational studies. Neuroepidemiology  2015; 44(1): 51-63.
[http://dx.doi.org/10.1159/000371710] [PMID: 25721193] 
[199] 
Ritchie K, Carrière I, de Mendonca A, et al. The neuroprotective effects of caffeine: A prospective population study (the Three City Study). Neurology  2007; 69(6): 536-45.
[http://dx.doi.org/10.1212/01.wnl.0000266670.35219.0c] [PMID: 17679672] 
[200] 
Lindsay J, Laurin D, Verreault R, et al. Risk factors for Alzheimer’s disease: A prospective analysis from the Canadian Study of Health and Aging. Am J Epidemiol  2002; 156(5): 445-53.
[http://dx.doi.org/10.1093/aje/kwf074] [PMID: 12196314] 
[201] 
Arendash GW, Cao C. Caffeine and coffee as therapeutics against Alzheimer’s disease. J Alzheimers Dis  2010; 20(s1)(Suppl. 1): S117-26.
[http://dx.doi.org/10.3233/JAD-2010-091249] [PMID: 20182037] 
[202] 
McKenzie S, Marley PD. Caffeine stimulates Ca(2+) entry through store-operated channels to activate tyrosine hydroxylase in bovine chromaffin cells. Eur J Neurosci  2002; 15(9): 1485-92.
[http://dx.doi.org/10.1046/j.1460-9568.2002.01990.x] [PMID: 12028358] 
[203] 
Yoshimura H. The potential of caffeine for functional modification from cortical synapses to neuron networks in the brain. Curr Neuropharmacol  2005; 3(4): 309-16.
[http://dx.doi.org/10.2174/157015905774322543] [PMID: 18369398] 
[204] 
Arendash GW, Mori T, Cao C, et al. Caffeine reverses cognitive impairment and decreases brain amyloid-β levels in aged Alzheimer’s disease mice. J Alzheimers Dis  2009; 17(3): 661-80.
[http://dx.doi.org/10.3233/JAD-2009-1087] [PMID: 19581722] 
[205] 
Garrett BE, Griffiths RR. The role of dopamine in the behavioral effects of caffeine in animals and humans. Pharmacol Biochem Behav  1997; 57(3): 533-41.
[http://dx.doi.org/10.1016/S0091-3057(96)00435-2] [PMID: 9218278] 
[206] 
Lee M, McGeer EG, McGeer PL. Quercetin, not caffeine, is a major neuroprotective component in coffee. Neurobiol Aging  2016; 46: 113-23.
[http://dx.doi.org/10.1016/j.neurobiolaging.2016.06.015] [PMID: 27479153] 
[207] 
Laitala VS, Kaprio J, Koskenvuo M, Räihä I, Rinne JO, Silventoinen K. Coffee drinking in middle age is not associated with cognitive performance in old age. Am J Clin Nutr  2009; 90(3): 640-6.
[http://dx.doi.org/10.3945/ajcn.2009.27660] [PMID: 19587088] 
[208] 
Majewski Ł, Maciąg F, Boguszewski PM, et al. Overexpression of STIM1 in neurons in mouse brain improves contextual learning and impairs long-term depression. Biochim Biophys Acta Mol Cell Res  2017; 1864(6): 1071-87.
[http://dx.doi.org/10.1016/j.bbamcr.2016.11.025] [PMID: 27913207] 
[209] 
Dumont M, Lin MT, Beal MF. Mitochondria and antioxidant targeted therapeutic strategies for Alzheimer’s disease. J Alzheimers Dis  20(2): S633-43.
[http://dx.doi.org/10.3233/JAD-2010-100507] 
[210] 
Picone P, Nuzzo D, Caruana L, Scafidi V, Di Carlo M. Mitochondrial dysfunction: different routes to Alzheimer’s disease therapy. Oxid Med Cell Longev  2014; 2014: 780179-9.
[http://dx.doi.org/10.1155/2014/780179] [PMID: 25221640] 
[211] 
Chakravorty A, Jetto CT, Manjithaya R. Dysfunctional mitochondria and mitophagy as drivers of Alzheimer’s disease pathogenesis. Front Aging Neurosci  2019; 11(311): 311.
[http://dx.doi.org/10.3389/fnagi.2019.00311] [PMID: 31824296] 
[212] 
Murphy MP, Hartley RC. Mitochondria as a therapeutic target for common pathologies. Nat Rev Drug Discov  2018; 17(12): 865-86.
[http://dx.doi.org/10.1038/nrd.2018.174] [PMID: 30393373] 
[213] 
Hung CH, Ho YS, Chang RC. Modulation of mitochondrial calcium as a pharmacological target for Alzheimer’s disease. Ageing Res Rev  2010; 9(4): 447-56.
[http://dx.doi.org/10.1016/j.arr.2010.05.003] [PMID: 20553970] 
[214] 
Calvo-Rodriguez M, Hernando-Perez E, Nuñez L, Villalobos C. Amyloid β oligomers increase ER-mitochondria Ca2+ cross talk in young hippocampal neurons and exacerbate aging-induced intracellular Ca2+ remodeling. Front Cell Neurosci  2019; 13: 22.
[http://dx.doi.org/10.3389/fncel.2019.00022] [PMID: 30800057] 
[215] 
Sánchez JA, Alfonso A, Leirós M, et al. Spongionella secondary metabolites regulate store operated calcium entry modulating mitochondrial functioning in SH-SY5Y neuroblastoma cells. Cell Physiol Biochem  2015; 37(2): 779-92.
[http://dx.doi.org/10.1159/000430395] [PMID: 26356268] 
[216] 
Kon N, Murakoshi M, Isobe A, Kagechika K, Miyoshi N, Nagayama T. DS16570511 is a small-molecule inhibitor of the mitochondrial calcium uniporter. Cell Death Discov  2017; 3(1): 17045.
[http://dx.doi.org/10.1038/cddiscovery.2017.45] [PMID: 28725491] 
[217] 
Kon N, Satoh A, Miyoshi N. A small-molecule DS44170716 inhibits Ca2+-induced mitochondrial permeability transition. Sci Rep  2017; 7(1): 3864.
[http://dx.doi.org/10.1038/s41598-017-03651-7] [PMID: 28634393] 
[218] 
Samanta K, Douglas S. Parekh ABJPo Mitochondrial calcium uniporter MCU supports cytoplasmic Ca2+ oscillations, store-operated Ca2+ entry and Ca2+-dependent gene expression in response to receptor stimulation  2014; 9(7)e101188
[219] 
Jaworska A, Dzbek J, Styczynska M, Kuznicki J. Analysis of calcium homeostasis in fresh lymphocytes from patients with sporadic Alzheimer’s disease or mild cognitive impairment. Biochim Biophys Acta  2013; 1833(7): 1692-9.
[http://dx.doi.org/10.1016/j.bbamcr.2013.01.012] [PMID: 23354174] 
[220] 
DeHaven WI, Smyth JT, Boyles RR, Bird GS, Putney JW Jr. Complex actions of 2-aminoethyldiphenyl borate on store-operated calcium entry. J Biol Chem  2008; 283(28): 19265-73.
[http://dx.doi.org/10.1074/jbc.M801535200] [PMID: 18487204] 
[221] 
Schindl R, Bergsmann J, Frischauf I, et al. 2-aminoethoxydiphenyl borate alters selectivity of Orai3 channels by increasing their pore size. J Biol Chem  2008; 283(29): 20261-7.
[http://dx.doi.org/10.1074/jbc.M803101200] [PMID: 18499656] 
[222] 
Hu W-Y, He ZY, Yang LJ, Zhang M, Xing D, Xiao ZC. The Ca2+ channel inhibitor 2-APB reverses β-amyloid-induced LTP deficit in hippocampus by blocking BAX and caspase-3 hyperactivation. Br J Pharmacol  2015; 172(9): 2273-85.
[http://dx.doi.org/10.1111/bph.13048] [PMID: 25521332] 
[223] 
Suen KC, Lin KF, Elyaman W, So KF, Chang RC, Hugon J. Reduction of calcium release from the endoplasmic reticulum could only provide partial neuroprotection against beta-amyloid peptide toxicity. J Neurochem  2003; 87(6): 1413-26.
[http://dx.doi.org/10.1111/j.1471-4159.2003.02259.x] [PMID: 14713297] 
[224] 
Zolezzi JM, Carvajal FJ, Ríos JA, et al. Tetrahydrohyperforin induces mitochondrial dynamics and prevents mitochondrial Ca2+ overload after Aβ and Aβ-AChE complex challenge in rat hippocampal neurons. J Alzheimers Dis  2013; 37(4): 735-46.
[http://dx.doi.org/10.3233/JAD-130173] [PMID: 23948911] 
[225] 
De Felice FG, Velasco PT, Lambert MP, 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 Biol Chem  2007; 282(15): 11590-601.
[http://dx.doi.org/10.1074/jbc.M607483200] [PMID: 17308309] 
[226] 
Li L, Sengupta A, Haque N, Grundke-Iqbal I, Iqbal K. Memantine inhibits and reverses the Alzheimer type abnormal hyperphosphorylation of tau and associated neurodegeneration. FEBS Lett  2004; 566(1-3): 261-9.
[http://dx.doi.org/10.1016/j.febslet.2004.04.047] [PMID: 15147906] 
[227] 
Administration, U.S.F.A.D.. Memantine approved for Alzheimer disease 2003.
[228] 
Joseph D. Method of treating amyloidosis by modulation of calcium 1996.
[229] 
Huang HM, Chen HL, Gibson GE. Interactions of endoplasmic reticulum and mitochondria Ca(2+) stores with capacitative calcium entry. Metab Brain Dis  2014; 29(4): 1083-93.
[http://dx.doi.org/10.1007/s11011-014-9541-4] [PMID: 24748364] 
[230] 
Akhter H, Katre A, Li L, Liu X, Liu RM. Therapeutic potential and anti-amyloidosis mechanisms of tert-butylhydroquinone for Alzheimer’s disease. J Alzheimers Dis  2011; 26(4): 767-78.
[http://dx.doi.org/10.3233/JAD-2011-110512] [PMID: 21860091] 
[231] 
Reed PW, Lardy HA. A23187: A divalent cation ionophore. J Biol Chem  1972; 247(21): 6970-7.
[PMID: 4263618] 
[232] 
Kodis EJ, Choi S, Swanson E, Ferreira G, Bloom GS. N-methyl-D-aspartate receptor-mediated calcium influx connects amyloid-β oligomers to ectopic neuronal cell cycle reentry in Alzheimer’s disease. Alzheimers Dement  2018; 14(10): 1302-12.
[http://dx.doi.org/10.1016/j.jalz.2018.05.017] [PMID: 30293574] 
[233] 
Hoth M, Penner R. Depletion of intracellular calcium stores activates a calcium current in mast cells. Nature  1992; 355(6358): 353-6.
[http://dx.doi.org/10.1038/355353a0] [PMID: 1309940] 
[234] 
Michael E. Cyclosporin a conjugates and uses therefor 2001.
[235] 
Guo L, Du H, Yan S, et al. Cyclophilin D deficiency rescues axonal mitochondrial transport in Alzheimer’s neurons. PLoS One  2013; 8(1)e54914
[http://dx.doi.org/10.1371/journal.pone.0054914] [PMID: 23382999] 
Rights & Permissions Print Cite
Article Metrics
24
1
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/1567205018666210119150613	Print ISSN 1567-2050
Publisher Name Bentham Science Publisher	Online ISSN 1875-5828
当代阿耳茨海默病研究

矫正储存操作性钙的减弱作为一种治疗阿尔茨海默氏病的方法

摘要

当代阿耳茨海默病研究

矫正储存操作性钙的减弱作为一种治疗阿尔茨海默氏病的方法

摘要 Play Pause

Related Journals

Related Books

Related Articles

摘要
