{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:39:25Z","timestamp":1790959165020,"version":"4.1.0"},"reference-count":66,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,4,25]],"date-time":"2020-04-25T00:00:00Z","timestamp":1587772800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,4,25]],"date-time":"2020-04-25T00:00:00Z","timestamp":1587772800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["EY027824"],"award-info":[{"award-number":["EY027824"]}]},{"name":"Missouri University","award":["Start-up"],"award-info":[{"award-number":["Start-up"]}]},{"name":"Linkoping University","award":["Ogonfonden Award"],"award-info":[{"award-number":["Ogonfonden Award"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The ways in which microglia activate and promote neovascularization (NV) are not fully understood. Recent in vivo evidence supports the theory that calcium is required for the transition of microglia from a surveillance state to an active one. The objectives of this study were to discover novel L-type voltage-gated channel (L-VGCC) blockers and investigate their application for the prevention of inflammation and angiogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Pharmacophore-based computational modeling methods were used to screen for novel calcium channel blockers (CCBs) from the ZINC compound library. The effects of CCBs on calcium blockade, microglial pro-inflammatory activation, and cell toxicity were validated in BV-2 microglial\u00a0cell and freshly isolated smooth muscle cell (SMC) cultures. Laser-induced choroidal neovascularization (NV) and the suture-induced inflammatory corneal NV models of angiogenesis were used for in vivo validation of the novel CCBs. CX3CR1<jats:sup>gfp\/+<\/jats:sup>mice were used to examine the infiltration of GFP-labeled microglial cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified three compounds from the ZINC database (Zinc20267861, Zinc18204217, and Zinc33254827) as new blockers of L-type voltage-gated calcium channels (L-VGCC) using a structure-based pharmacophore approach. The effects of the three CCBs on Ca<jats:sup>2+<\/jats:sup>influx into cells were verified in BV-2 microglial cells using Fura-2 fluorescent dye and in freshly isolated SMCs using the voltage-patch clamp. All three CCBs reduced microglial cell migration, activation stimulated by lipopolysaccharide (LPS), and reduced the expression of the inflammatory markers NF-\u03baB (phospho-I\u03baB\u03b1) and cyclooxygenase-2 (COX-2) as well as reactive oxygen species. Of the three compounds, we further examined the in vivo activity of Zinc20267861. Topical treatment with Zinc20267861 in a rat model of suture-induced inflammatory cornea neovascularization demonstrated efficacy of the compound in reducing monocyte infiltration and overall corneal NV response. Subconjunctival administration of the compound in the choroidal NV mouse model effectively prevented CNV and microglial infiltration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings suggest that the novel CCBs identified here are effective anti-inflammatory agents that can be further evaluated for treating NV disorders and can be potentially applied in the treatment of ocular inflammatory and pathological angiogenetic disorders.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12974-020-01801-9","type":"journal-article","created":{"date-parts":[[2020,4,25]],"date-time":"2020-04-25T10:02:48Z","timestamp":1587808968000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Discovery of novel L-type voltage-gated calcium channel blockers and application for the prevention of inflammation and angiogenesis"],"prefix":"10.1186","volume":"17","author":[{"given":"Madhu Sudhana","family":"Saddala","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Lennikov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Mukwaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Hill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Lagali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,4,25]]},"reference":[{"key":"1801_CR1","doi-asserted-by":"publisher","first-page":"140","DOI":"10.3389\/fnagi.2018.00140","volume":"10","author":"V Navarro","year":"2018","unstructured":"Navarro V, Sanchez-Mejias E, Jimenez S, Munoz-Castro C, Sanchez-Varo R, Davila JC, et al. Microglia in Alzheimer\u2019s disease: activated, dysfunctional or degenerative. Front Aging Neurosci. 2018;10:140.","journal-title":"Front Aging Neurosci."},{"key":"1801_CR2","doi-asserted-by":"publisher","first-page":"401264","DOI":"10.1155\/2012\/401264","volume":"2012","author":"LJ Peterson","year":"2012","unstructured":"Peterson LJ, Flood PM. Oxidative stress and microglial cells in Parkinson\u2019s disease. Mediators Inflamm. 2012;2012:401264.","journal-title":"Mediators Inflamm."},{"issue":"3","key":"1801_CR3","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1007\/s12026-008-8018-0","volume":"41","author":"L Qian","year":"2008","unstructured":"Qian L, Flood PM. Microglial cells and Parkinson\u2019s disease. Immunol Res. 2008;41(3):155\u201364.","journal-title":"Immunol Res."},{"key":"1801_CR4","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.2147\/NDT.S140634","volume":"13","author":"C Luo","year":"2017","unstructured":"Luo C, Jian C, Liao Y, Huang Q, Wu Y, Liu X, et al. The role of microglia in multiple sclerosis. Neuropsychiatr Dis Treat. 2017;13:1661\u20137.","journal-title":"Neuropsychiatr Dis Treat."},{"issue":"3","key":"1801_CR5","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1007\/s11910-005-0052-x","volume":"5","author":"X Deng","year":"2005","unstructured":"Deng X, Sriram S. Role of microglia in multiple sclerosis. Curr Neurol Neurosci Rep. 2005;5(3):239\u201344.","journal-title":"Curr Neurol Neurosci Rep."},{"issue":"6","key":"1801_CR6","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1038\/nri3459","volume":"13","author":"J Ambati","year":"2013","unstructured":"Ambati J, Atkinson JP, Gelfand BD. Immunology of age-related macular degeneration. Nat Rev Immunol. 2013;13(6):438\u201351.","journal-title":"Nat Rev Immunol."},{"issue":"3","key":"1801_CR7","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.ceca.2012.12.003","volume":"53","author":"B Brawek","year":"2013","unstructured":"Brawek B, Garaschuk O. Microglial calcium signaling in the adult, aged and diseased brain. Cell Calcium. 2013;53(3):159\u201369.","journal-title":"Cell Calcium."},{"key":"1801_CR8","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.mcn.2014.12.004","volume":"64","author":"JF Espinosa-Parrilla","year":"2015","unstructured":"Espinosa-Parrilla JF, Martinez-Moreno M, Gasull X, Mahy N, Rodriguez MJ. The L-type voltage-gated calcium channel modulates microglial pro-inflammatory activity. Mol Cell Neurosci. 2015;64:104\u201315.","journal-title":"Mol Cell Neurosci."},{"issue":"6","key":"1801_CR9","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1097\/00005344-200106000-00002","volume":"37","author":"V Leuranguer","year":"2001","unstructured":"Leuranguer V, Mangoni ME, Nargeot J, Richard S. Inhibition of T-type and L-type calcium channels by mibefradil: physiologic and pharmacologic bases of cardiovascular effects. J Cardiovasc Pharmacol. 2001;37(6):649\u201361.","journal-title":"J Cardiovasc Pharmacol."},{"key":"1801_CR10","doi-asserted-by":"publisher","first-page":"45211","DOI":"10.1038\/srep45211","volume":"7","author":"MS Saddala","year":"2017","unstructured":"Saddala MS, Kandimalla R, Adi PJ, Bhashyam SS, Asupatri UR. Novel 1, 4-dihydropyridines for L-type calcium channel as antagonists for cadmium toxicity. Sci Rep. 2017;7:45211.","journal-title":"Sci Rep."},{"issue":"1","key":"1801_CR11","doi-asserted-by":"publisher","first-page":"44","DOI":"10.2174\/187152711794488638","volume":"10","author":"SD Skaper","year":"2011","unstructured":"Skaper SD. Ion channels on microglia: therapeutic targets for neuroprotection. CNS Neurol Disord Drug Targets. 2011;10(1):44\u201356.","journal-title":"CNS Neurol Disord Drug Targets."},{"key":"1801_CR12","doi-asserted-by":"publisher","first-page":"497","DOI":"10.3389\/fimmu.2015.00497","volume":"6","author":"MJ Stebbing","year":"2015","unstructured":"Stebbing MJ, Cottee JM, Rana I. The role of ion channels in microglial activation and proliferation - a complex interplay between ligand-gated ion channels, K(+) channels, and intracellular Ca(2.). Front Immunol. 2015;6:497.","journal-title":"Front Immunol"},{"key":"1801_CR13","first-page":"e53502","volume":"106","author":"RS Shah","year":"2015","unstructured":"Shah RS, Soetikno BT, Lajko M, Fawzi AA. A Mouse model for laser-induced choroidal neovascularization. J Vis Exp. 2015;106:e53502.","journal-title":"J Vis Exp."},{"issue":"2","key":"1801_CR14","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1007\/s10456-018-9604-y","volume":"21","author":"A Mukwaya","year":"2018","unstructured":"Mukwaya A, Lennikov A, Xeroudaki M, Mirabelli P, Lachota M, Jensen L, et al. Time-dependent LXR\/RXR pathway modulation characterizes capillary remodeling in inflammatory corneal neovascularization. Angiogenesis. 2018;21(2):395\u2013413.","journal-title":"Angiogenesis."},{"issue":"2","key":"1801_CR15","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1007\/s10456-018-9594-9","volume":"21","author":"A Lennikov","year":"2018","unstructured":"Lennikov A, Mirabelli P, Mukwaya A, Schaupper M, Thangavelu M, Lachota M, et al. Selective IKK2 inhibitor IMD0354 disrupts NF-kappaB signaling to suppress corneal inflammation and angiogenesis. Angiogenesis. 2018;21(2):267\u201385.","journal-title":"Angiogenesis."},{"key":"1801_CR16","doi-asserted-by":"publisher","first-page":"160103","DOI":"10.1038\/sdata.2016.103","volume":"3","author":"A Mukwaya","year":"2016","unstructured":"Mukwaya A, Lindvall JM, Xeroudaki M, Peebo B, Ali Z, Lennikov A, et al. A microarray whole-genome gene expression dataset in a rat model of inflammatory corneal angiogenesis. Sci Data. 2016;3:160103.","journal-title":"Sci Data."},{"issue":"11","key":"1801_CR17","doi-asserted-by":"publisher","first-page":"388","DOI":"10.6026\/97320630013388","volume":"13","author":"MS Latha","year":"2017","unstructured":"Latha MS, Saddala MS. Molecular docking based screening of a simulated HIF-1 protein model for potential inhibitors. Bioinformation. 2017;13(11):388\u201393.","journal-title":"Bioinformation."},{"issue":"1","key":"1801_CR18","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1021\/ci049885e","volume":"45","author":"G Wolber","year":"2005","unstructured":"Wolber G, Langer T. LigandScout: 3-D pharmacophores derived from protein-bound ligands and their use as virtual screening filters. J Chem Inf Model. 2005;45(1):160\u20139.","journal-title":"J Chem Inf Model."},{"issue":"5","key":"1801_CR19","doi-asserted-by":"publisher","first-page":"e00612","DOI":"10.1016\/j.heliyon.2018.e00612","volume":"4","author":"MS Saddala","year":"2018","unstructured":"Saddala MS, Adi PJ. Discovery of small molecules through pharmacophore modeling, docking and molecular dynamics simulation against Plasmodium vivax Vivapain-3 (VP-3). Heliyon. 2018;4(5):e00612.","journal-title":"Heliyon."},{"issue":"5","key":"1801_CR20","doi-asserted-by":"publisher","first-page":"1849","DOI":"10.1021\/ci049844i","volume":"44","author":"T Steindl","year":"2004","unstructured":"Steindl T, Langer T. Influenza virus neuraminidase inhibitors: generation and comparison of structure-based and common feature pharmacophore hypotheses and their application in virtual screening. J Chem Inf Comput Sci. 2004;44(5):1849\u201356.","journal-title":"J Chem Inf Comput Sci."},{"issue":"2","key":"1801_CR21","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","volume":"31","author":"O Trott","year":"2010","unstructured":"Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010;31(2):455\u201361.","journal-title":"J Comput Chem."},{"issue":"4","key":"1801_CR22","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1007\/BF00228148","volume":"8","author":"RA Laskowski","year":"1996","unstructured":"Laskowski RA, Rullmannn JA, MacArthur MW, Kaptein R, Thornton JM. AQUA and PROCHECK-NMR: programs for checking the quality of protein structures solved by NMR. J Biomol NMR. 1996;8(4):477\u201386.","journal-title":"J Biomol NMR."},{"issue":"1-3","key":"1801_CR23","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/S0169-409X(00)00129-0","volume":"46","author":"CA Lipinski","year":"2001","unstructured":"Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001;46(1-3):3\u201326.","journal-title":"Adv Drug Deliv Rev."},{"issue":"20","key":"1801_CR24","doi-asserted-by":"publisher","first-page":"3714","DOI":"10.1021\/jm000942e","volume":"43","author":"P Ertl","year":"2000","unstructured":"Ertl P, Rohde B, Selzer P. Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties. J Med Chem. 2000;43(20):3714\u20137.","journal-title":"J Med Chem."},{"issue":"10","key":"1801_CR25","doi-asserted-by":"publisher","first-page":"1446","DOI":"10.1023\/A:1020444330011","volume":"19","author":"YH Zhao","year":"2002","unstructured":"Zhao YH, Abraham MH, Le J, Hersey A, Luscombe CN, Beck G, et al. Rate-limited steps of human oral absorption and QSAR studies. Pharmaceutical research. 2002;19(10):1446\u201357.","journal-title":"Pharmaceutical research."},{"issue":"Pt 12","key":"1801_CR26","doi-asserted-by":"publisher","first-page":"3025","DOI":"10.1113\/jphysiol.2009.169920","volume":"587","author":"Y Yang","year":"2009","unstructured":"Yang Y, Murphy TV, Ella SR, Grayson TH, Haddock R, Hwang YT, et al. Heterogeneity in function of small artery smooth muscle BKCa: involvement of the beta1-subunit. J Physiol. 2009;587(Pt 12):3025\u201344.","journal-title":"J Physiol."},{"issue":"9","key":"1801_CR27","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.1038\/nm.2891","volume":"18","author":"A McCurley","year":"2012","unstructured":"McCurley A, Pires PW, Bender SB, Aronovitz M, Zhao MJ, Metzger D, et al. Direct regulation of blood pressure by smooth muscle cell mineralocorticoid receptors. Nat Med. 2012;18(9):1429\u201333.","journal-title":"Nat Med."},{"issue":"11","key":"1801_CR28","doi-asserted-by":"publisher","first-page":"4461","DOI":"10.1210\/en.2014-1270","volume":"155","author":"K Barrett Mueller","year":"2014","unstructured":"Barrett Mueller K, Lu Q, Mohammad NN, Luu V, McCurley A, Williams GH, et al. Estrogen receptor inhibits mineralocorticoid receptor transcriptional regulatory function. Endocrinology. 2014;155(11):4461\u201372.","journal-title":"Endocrinology."},{"key":"1801_CR29","first-page":"455","volume":"18","author":"A Lennikov","year":"2012","unstructured":"Lennikov A, Kitaichi N, Fukase R, Murata M, Noda K, Ando R, et al. Amelioration of ultraviolet-induced photokeratitis in mice treated with astaxanthin eye drops. Mol Vis. 2012;18:455\u201364.","journal-title":"Mol Vis."},{"issue":"8","key":"1801_CR30","doi-asserted-by":"publisher","first-page":"e71808","DOI":"10.1371\/journal.pone.0071808","volume":"8","author":"H Huang","year":"2013","unstructured":"Huang H, Parlier R, Shen JK, Lutty GA, Vinores SA. VEGF receptor blockade markedly reduces retinal microglia\/macrophage infiltration into laser-induced CNV. PLoS One. 2013;8(8):e71808.","journal-title":"PLoS One."},{"issue":"6","key":"1801_CR31","doi-asserted-by":"publisher","first-page":"3060","DOI":"10.1167\/iovs.10-6101","volume":"52","author":"BB Peebo","year":"2011","unstructured":"Peebo BB, Fagerholm P, Traneus-R\u00f6ckert C, Lagali N. Time-lapse in vivo imaging of corneal angiogenesis: the role of inflammatory cells in capillary sprouting. Invest Ophthalmol Vis Sci. 2011;52(6):3060\u20138.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"1801_CR32","doi-asserted-by":"publisher","first-page":"32137","DOI":"10.1038\/srep32137","volume":"6","author":"A Mukwaya","year":"2016","unstructured":"Mukwaya A, Peebo B, Xeroudaki M, Ali Z, Lennikov A, Jensen L, et al. Factors regulating capillary remodeling in a reversible model of inflammatory corneal angiogenesis. Sci Rep. 2016;6:32137.","journal-title":"Sci Rep"},{"issue":"2","key":"1801_CR33","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1007\/s10456-018-9594-9","volume":"21","author":"A Lennikov","year":"2018","unstructured":"Lennikov A, Mirabelli P, Mukwaya A, Schaupper M, Thangavelu M, Lachota M, et al. Selective IKK2 inhibitor IMD0354 disrupts NF-\u03baB signaling to suppress corneal inflammation and angiogenesis. Angiogenesis. 2018;21(2):267\u201385.","journal-title":"Angiogenesis."},{"issue":"8","key":"1801_CR34","doi-asserted-by":"publisher","first-page":"2990","DOI":"10.1167\/iovs.19-27591","volume":"60","author":"A Mukwaya","year":"2019","unstructured":"Mukwaya A, Mirabelli P, Lennikov A, Thangavelu M, Jensen L, Peebo B, et al. Repeat corneal neovascularization is characterized by more aggressive inflammation and vessel invasion than in the initial phase. Invest Ophthalmol Vis Sci. 2019;60(8):2990\u20133001.","journal-title":"Invest Ophthalmol Vis Sci."},{"issue":"1-2","key":"1801_CR35","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.drudis.2011.10.023","volume":"17","author":"G Moroy","year":"2012","unstructured":"Moroy G, Martiny VY, Vayer P, Villoutreix BO, Miteva MA. Toward in silico structure-based ADMET prediction in drug discovery. Drug Discov Today. 2012;17(1-2):44\u201355.","journal-title":"Drug Discov Today."},{"key":"1801_CR36","first-page":"447","volume":"9","author":"Z Yousuf","year":"2017","unstructured":"Yousuf Z, Iman K, Iftikhar N, Mirza MU. Structure-based virtual screening and molecular docking for the identification of potential multi-targeted inhibitors against breast cancer. Breast Cancer (Dove Med Press). 2017;9:447\u201359.","journal-title":"Breast Cancer (Dove Med Press)"},{"issue":"45","key":"1801_CR37","doi-asserted-by":"publisher","first-page":"23645","DOI":"10.1074\/jbc.M116.732610","volume":"291","author":"SH Lee","year":"2016","unstructured":"Lee SH, Sud N, Lee N, Subramaniyam S, Chung CY. Regulation of integrin alpha6 recycling by calcium-independent phospholipase A2 (iPLA2) to promote microglia chemotaxis on laminin. J Biol Chem. 2016;291(45):23645\u201353.","journal-title":"J Biol Chem."},{"key":"1801_CR38","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1186\/1742-2094-10-75","volume":"10","author":"S Lively","year":"2013","unstructured":"Lively S, Schlichter LC. The microglial activation state regulates migration and roles of matrix-dissolving enzymes for invasion. J Neuroinflammation. 2013;10:75.","journal-title":"J Neuroinflammation."},{"key":"1801_CR39","doi-asserted-by":"crossref","unstructured":"Tvrdik P, Kalani MYS. In vivo imaging of microglial calcium signaling in brain inflammation and injury. Int J Mol Sci. 2017;18(11).","DOI":"10.3390\/ijms18112366"},{"key":"1801_CR40","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1186\/1742-2094-11-98","volume":"11","author":"JD Cherry","year":"2014","unstructured":"Cherry JD, Olschowka JA, O'Banion MK. Neuroinflammation and M2 microglia: the good, the bad, and the inflamed. J Neuroinflamm. 2014;11:98.","journal-title":"J Neuroinflamm"},{"key":"1801_CR41","doi-asserted-by":"publisher","first-page":"739","DOI":"10.3389\/fpsyt.2018.00739","volume":"9","author":"C Culmsee","year":"2018","unstructured":"Culmsee C, Michels S, Scheu S, Arolt V, Dannlowski U, Alferink J. Mitochondria, microglia, and the immune system-how are they linked in affective disorders? Front Psychiatry. 2018;9:739.","journal-title":"Front Psychiatry."},{"issue":"8","key":"1801_CR42","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1080\/10641960802580190","volume":"30","author":"F Amenta","year":"2008","unstructured":"Amenta F, Tomassoni D, Traini E, Mignini F, Veglio F. Nicardipine: a hypotensive dihydropyridine-type calcium antagonist with a peculiar cerebrovascular profile. Clin Exp Hypertens. 2008;30(8):808\u201326.","journal-title":"Clin Exp Hypertens."},{"issue":"2","key":"1801_CR43","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1016\/j.bbrc.2010.04.149","volume":"396","author":"T Matsui","year":"2010","unstructured":"Matsui T, Takeuchi M, Yamagishi S. Nifedipine, a calcium channel blocker, inhibits inflammatory and fibrogenic gene expressions in advanced glycation end product (AGE)-exposed fibroblasts via mineralocorticoid receptor antagonistic activity. Biochem Biophys Res Commun. 2010;396(2):566\u201370.","journal-title":"Biochem Biophys Res Commun."},{"issue":"4","key":"1801_CR44","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/j.neuropharm.2012.05.033","volume":"63","author":"S Hashioka","year":"2012","unstructured":"Hashioka S, Klegeris A, McGeer PL. Inhibition of human astrocyte and microglia neurotoxicity by calcium channel blockers. Neuropharmacology. 2012;63(4):685\u201391.","journal-title":"Neuropharmacology."},{"issue":"2-3","key":"1801_CR45","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/j.neuropharm.2010.10.002","volume":"60","author":"Y Liu","year":"2011","unstructured":"Liu Y, Lo YC, Qian L, Crews FT, Wilson B, Chen HL, et al. Verapamil protects dopaminergic neuron damage through a novel anti-inflammatory mechanism by inhibition of microglial activation. Neuropharmacology. 2011;60(2-3):373\u201380.","journal-title":"Neuropharmacology."},{"issue":"1","key":"1801_CR46","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.brainresbull.2011.10.004","volume":"87","author":"JA Smith","year":"2012","unstructured":"Smith JA, Das A, Ray SK, Banik NL. Role of pro-inflammatory cytokines released from microglia in neurodegenerative diseases. Brain Res Bull. 2012;87(1):10\u201320.","journal-title":"Brain Res Bull."},{"key":"1801_CR47","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1146\/annurev-physiol-022516-034406","volume":"79","author":"SA Wolf","year":"2017","unstructured":"Wolf SA, Boddeke HW, Kettenmann H. Microglia in physiology and disease. Annu Rev Physiol. 2017;79:619\u201343.","journal-title":"Annu Rev Physiol."},{"issue":"2","key":"1801_CR48","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1152\/physrev.00011.2010","volume":"91","author":"H Kettenmann","year":"2011","unstructured":"Kettenmann H, Hanisch UK, Noda M, Verkhratsky A. Physiology of microglia. Physiol Rev. 2011;91(2):461\u2013553.","journal-title":"Physiol Rev."},{"issue":"11","key":"1801_CR49","doi-asserted-by":"publisher","first-page":"4410","DOI":"10.1523\/JNEUROSCI.23-11-04410.2003","volume":"23","author":"A Hoffmann","year":"2003","unstructured":"Hoffmann A, Kann O, Ohlemeyer C, Hanisch UK, Kettenmann H. Elevation of basal intracellular calcium as a central element in the activation of brain macrophages (microglia): suppression of receptor-evoked calcium signaling and control of release function. J Neurosci. 2003;23(11):4410\u20139.","journal-title":"J Neurosci."},{"issue":"10","key":"1801_CR50","doi-asserted-by":"publisher","first-page":"e25916","DOI":"10.1371\/journal.pone.0025916","volume":"6","author":"J Anrather","year":"2011","unstructured":"Anrather J, Gallo EF, Kawano T, Orio M, Abe T, Gooden C, et al. Purinergic signaling induces cyclooxygenase-1-dependent prostanoid synthesis in microglia: roles in the outcome of excitotoxic brain injury. PLoS One. 2011;6(10):e25916.","journal-title":"PLoS One."},{"issue":"5","key":"1801_CR51","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1007\/s00424-006-0064-7","volume":"452","author":"K Farber","year":"2006","unstructured":"Farber K, Kettenmann H. Purinergic signaling and microglia. Pflugers Arch. 2006;452(5):615\u201321.","journal-title":"Pflugers Arch."},{"issue":"3","key":"1801_CR52","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1016\/j.neuropharm.2008.10.016","volume":"56","author":"Y Li","year":"2009","unstructured":"Li Y, Hu X, Liu Y, Bao Y, An L. Nimodipine protects dopaminergic neurons against inflammation-mediated degeneration through inhibition of microglial activation. Neuropharmacology. 2009;56(3):580\u20139.","journal-title":"Neuropharmacology."},{"key":"1801_CR53","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1186\/s12974-014-0158-7","volume":"11","author":"JL Furman","year":"2014","unstructured":"Furman JL, Norris CM. Calcineurin and glial signaling: neuroinflammation and beyond. J Neuroinflammation. 2014;11:158.","journal-title":"J Neuroinflammation."},{"key":"1801_CR54","first-page":"619050","volume":"2014","author":"F Wang","year":"2014","unstructured":"Wang F, Liu DZ, Xu H, Li Y, Wang W, Liu BL, et al. Thapsigargin induces apoptosis by impairing cytoskeleton dynamics in human lung adenocarcinoma cells. Sci World J. 2014;2014:619050.","journal-title":"Sci World J"},{"issue":"8","key":"1801_CR55","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1007\/s00232-014-9689-1","volume":"247","author":"E Mostafavi","year":"2014","unstructured":"Mostafavi E, Nargesi AA, Ghazizadeh Z, Larry M, Farahani RH, Morteza A, et al. The degree of resistance of erythrocyte membrane cytoskeletal proteins to supra-physiologic concentrations of calcium: an in vitro study. J Membr Biol. 2014;247(8):695\u2013701.","journal-title":"J Membr Biol."},{"issue":"2","key":"1801_CR56","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/0014-5793(86)81061-4","volume":"208","author":"Y Ohta","year":"1986","unstructured":"Ohta Y, Nishida E, Sakai H. Type II Ca2+\/calmodulin-dependent protein kinase binds to actin filaments in a calmodulin-sensitive manner. FEBS Lett. 1986;208(2):423\u20136.","journal-title":"FEBS Lett."},{"issue":"7","key":"1801_CR57","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1021\/bi3016586","volume":"52","author":"L Hoffman","year":"2013","unstructured":"Hoffman L, Farley MM, Waxham MN. Calcium-calmodulin-dependent protein kinase II isoforms differentially impact the dynamics and structure of the actin cytoskeleton. Biochemistry. 2013;52(7):1198\u2013207.","journal-title":"Biochemistry."},{"issue":"41","key":"1801_CR58","doi-asserted-by":"publisher","first-page":"16176","DOI":"10.1073\/pnas.0707719104","volume":"104","author":"JH Evans","year":"2007","unstructured":"Evans JH, Falke JJ. Ca2+ influx is an essential component of the positive-feedback loop that maintains leading-edge structure and activity in macrophages. Proc Natl Acad Sci U S A. 2007;104(41):16176\u201381.","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"5651","key":"1801_CR59","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.1126\/science.1092053","volume":"302","author":"AJ Ridley","year":"2003","unstructured":"Ridley AJ, Schwartz MA, Burridge K, Firtel RA, Ginsberg MH, Borisy G, et al. Cell migration: integrating signals from front to back. Science. 2003;302(5651):1704\u20139.","journal-title":"Science."},{"issue":"2","key":"1801_CR60","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/j.cell.2007.01.051","volume":"129","author":"CB Guan","year":"2007","unstructured":"Guan CB, Xu HT, Jin M, Yuan XB, Poo MM. Long-range Ca2+ signaling from growth cone to soma mediates reversal of neuronal migration induced by slit-2. Cell. 2007;129(2):385\u201395.","journal-title":"Cell."},{"issue":"5","key":"1801_CR61","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1016\/j.devcel.2012.09.021","volume":"23","author":"S Marion","year":"2012","unstructured":"Marion S, Mazzolini J, Herit F, Bourdoncle P, Kambou-Pene N, Hailfinger S, et al. The NF-kappaB signaling protein Bcl10 regulates actin dynamics by controlling AP1 and OCRL-bearing vesicles. Dev Cell. 2012;23(5):954\u201367.","journal-title":"Dev Cell."},{"issue":"24","key":"1801_CR62","doi-asserted-by":"publisher","first-page":"4163","DOI":"10.1007\/s00018-012-1072-8","volume":"69","author":"M Muik","year":"2012","unstructured":"Muik M, Schindl R, Fahrner M, Romanin C. Ca(2+) release-activated Ca(2+) (CRAC) current, structure, and function. Cell Mol Life Sci. 2012;69(24):4163\u201376.","journal-title":"Cell Mol Life Sci."},{"issue":"22","key":"1801_CR63","doi-asserted-by":"publisher","first-page":"6027","DOI":"10.1093\/emboj\/cdg583","volume":"22","author":"S Moosmang","year":"2003","unstructured":"Moosmang S, Schulla V, Welling A, Feil R, Feil S, Wegener JW, et al. Dominant role of smooth muscle L-type calcium channel Cav1.2 for blood pressure regulation. EMBO J. 2003;22(22):6027\u201334.","journal-title":"EMBO J."},{"issue":"7","key":"1801_CR64","doi-asserted-by":"publisher","first-page":"262","DOI":"10.4049\/immunohorizons.1900038","volume":"3","author":"M Burgess","year":"2019","unstructured":"Burgess M, Wicks K, Gardasevic M, Mace KA. Cx3CR1 expression identifies distinct macrophage populations that contribute differentially to inflammation and repair. Immunohorizons. 2019;3(7):262\u201373.","journal-title":"Immunohorizons."},{"issue":"1","key":"1801_CR65","doi-asserted-by":"publisher","first-page":"e5-e","DOI":"10.4110\/in.2018.18.e5","volume":"18","author":"M Lee","year":"2018","unstructured":"Lee M, Lee Y, Song J, Lee J, Chang S-Y. Tissue-specific Role of CX(3)CR1 Expressing immune cells and their relationships with human disease. Immune Netw. 2018;18(1):e5-e.","journal-title":"Immune Netw"},{"issue":"12","key":"1801_CR66","doi-asserted-by":"publisher","first-page":"E1738","DOI":"10.1073\/pnas.1525528113","volume":"113","author":"ML Bennett","year":"2016","unstructured":"Bennett ML, Bennett FC, Liddelow SA, Ajami B, Zamanian JL, Fernhoff NB, et al. New tools for studying microglia in the mouse and human CNS. Proc Natl Acad Sci U S A. 2016;113(12):E1738\u201346.","journal-title":"Proc Natl Acad Sci U S A."}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-020-01801-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12974-020-01801-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-020-01801-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,4]],"date-time":"2024-08-04T18:18:13Z","timestamp":1722795493000},"score":1,"resource":{"primary":{"URL":"https:\/\/jneuroinflammation.biomedcentral.com\/articles\/10.1186\/s12974-020-01801-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,25]]},"references-count":66,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["1801"],"URL":"https:\/\/doi.org\/10.1186\/s12974-020-01801-9","relation":{},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,25]]},"assertion":[{"value":"20 May 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 April 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 April 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All experiments were approved by the Institutional Animal Care and Use Committee of the University of Missouri School of Medicine (protocol number: 9520) and were in accordance with the guidelines of the Association for Research in Vision and Ophthalmology Statement for the use of animals in ophthalmic and vision research.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"132"}}