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Review Article

信号转导途径是南美锥虫病的治疗目标

卷 26, 期 36, 2019

页: [6572 - 6589] 页: 18

弟呕挨: 10.2174/0929867326666190620093029

价格: $65

摘要

锥虫是一组带鞭毛的单细胞真核生物，引起严重的人类疾病，包括南美锥虫病（Trypanosoma cruzi），昏睡病（Trypanosoma brucei spp。）和利什曼病（Leishmania spp。）。第二信使cAMP参与了这些寄生虫的许多基本过程，包括阶段之间的区分，增殖，渗透调节，氧化应激和群体感应。有趣的是，它的信号传导途径与哺乳动物完全不同，包括结构上不同的腺苷酸环化酶，直系同源效应蛋白的缺乏和G蛋白偶联受体的缺乏等。这些特征使参与这些转导途径的蛋白质成为治疗靶标的良好候选者。但是，鉴定新的未知药物靶标需要花费大量的研究时间，并且在经济上非常昂贵，这使得从基础研究过渡到临床阶段变得困难。锥虫的PDE具有特征性的结合口袋，可从其人类直系同源物上获得不同的抑制作用。修改批准用于人类的药物以将其转化为锥虫治疗可以导致更有效的治疗，更短的实验室时间和更低的成本。鉴于运动质体PDE与哺乳动物的PDE高度保守，并且由于市场上已经有许多针对人类PDE的药物，因此药物重新定位方法非常有前途。新技术的发展，政府和产业界的更多参与以及更多致力于基础研究的科学家，是最终找到有效治疗和治愈被忽视的热带病的关键。

关键词: 克氏锥虫，布鲁氏锥虫，利什曼原虫属，cAMP，腺苷酸环化酶，磷酸二酯酶，治疗靶标，药物重新定位

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[1]
Pérez-Molina, J.A.; Molina, I. Chagas disease. Lancet, 2018, 391(10115), 82-94.
[http://dx.doi.org/10.1016/S0140-6736(17)31612-4] [PMID: 28673423]
[2]
Trouiller, P.; Olliaro, P.; Torreele, E.; Orbinski, J.; Laing, R.; Ford, N. Drug development for neglected diseases: a deficient market and a public-health policy failure. Lancet, 2002, 359(9324), 2188-2194.
[http://dx.doi.org/10.1016/S0140-6736(02)09096-7] [PMID: 12090998]
[3]
Field, M.C.; Horn, D.; Fairlamb, A.H.; Ferguson, M.A.J.; Gray, D.W.; Read, K.D.; De Rycker, M.; Torrie, L.S.; Wyatt, P.G.; Wyllie, S.; Gilbert, I.H. Anti-trypanosomatid drug discovery: an ongoing challenge and a continuing need. Nat. Rev. Microbiol., 2017, 15(7), 447-447.
[http://dx.doi.org/10.1038/nrmicro.2017.69] [PMID: 28579611]
[4]
Bellera, C.L.; Sbaraglini, M.L.; Balcazar, D.E.; Fraccaroli, L.; Vanrell, M.C.; Casassa, A.F.; Labriola, C.A.; Romano, P.S.; Carrillo, C.; Talevi, A. High-throughput drug repositioning for the discovery of new treatments for Chagas disease. Mini Rev. Med. Chem., 2015, 15(3), 182-193.
[http://dx.doi.org/10.2174/138955751503150312120208] [PMID: 25769967]
[5]
Makin, L.; Gluenz, E. cAMP signalling in trypanosomatids: role in pathogenesis and as a drug target. Trends Parasitol., 2015, 31(8), 373-379.
[http://dx.doi.org/10.1016/j.pt.2015.04.014] [PMID: 26004537]
[6]
Braga, M.V.; de Souza, W. Effects of protein kinase and phosphatidylinositol-3 kinase inhibitors on growth and ultrastructure of Trypanosoma cruzi. FEMS Microbiol. Lett., 2006, 256(2), 209-216.
[http://dx.doi.org/10.1111/j.1574-6968.2006.00125.x] [PMID: 16499608]
[7]
Schoijet, A.C.; Sternlieb, T.; Alonso, G.D. The phosphatidylinositol 3-kinase class III complex containing TcVps15 and TcVps34 participates in autophagy in trypanosoma cruzi. J. Eukaryot. Microbiol., 2017, 64(3), 308-321.
[http://dx.doi.org/10.1111/jeu.12367] [PMID: 27603757]
[8]
Chiurillo, M.A.; Lander, N.; Bertolini, M.S.; Storey, M.; Vercesi, A.E.; Docampo, R. Different roles of mitochondrial calcium uniporter complex subunits in growth and infectivity of trypanosoma cruzi. MBio, 2017, 8(3), 1-16.
[http://dx.doi.org/10.1128/mBio.00574-17] [PMID: 28487431]
[9]
D’Angelo, M.A.; Montagna, A.E.; Sanguineti, S.; Torres, H.N.; Flawiá, M.M. A novel calcium-stimulated adenylyl cyclase from Trypanosoma cruzi, which interacts with the structural flagellar protein paraflagellar rod. J. Biol. Chem., 2002, 277(38), 35025-35034.
[http://dx.doi.org/10.1074/jbc.M204696200] [PMID: 12121994]
[10]
Paiva, C.N.; Medei, E.; Bozza, M.T. ROS and Trypanosoma cruzi: Fuel to infection, poison to the heart. PLoS Pathog., 2018, 14(4)e1006928
[http://dx.doi.org/10.1371/journal.ppat.1006928] [PMID: 29672619]
[11]
Graça-Souza, A.V.; Maya-Monteiro, C.; Paiva-Silva, G.O.; Braz, G.R.; Paes, M.C.; Sorgine, M.H.; Oliveira, M.F.; Oliveira, P.L. Adaptations against heme toxicity in blood-feeding arthropods. Insect Biochem. Mol. Biol., 2006, 36(4), 322-335.
[http://dx.doi.org/10.1016/j.ibmb.2006.01.009] [PMID: 16551546]
[12]
Castro, D.P.; Moraes, C.S.; Gonzalez, M.S.; Ratcliffe, N.A.; Azambuja, P.; Garcia, E.S. Trypanosoma cruzi immune response modulation decreases microbiota in Rhodnius prolixus gut and is crucial for parasite survival and development. PLoS One, 2012, 7(5)e36591
[http://dx.doi.org/10.1371/journal.pone.0036591] [PMID: 22574189]
[13]
Balla, T. Phosphoinositides: tiny lipids with giant impact on cell regulation. Physiol. Rev., 2013, 93(3), 1019-1137.
[http://dx.doi.org/10.1152/physrev.00028.2012] [PMID: 23899561]
[14]
Marat, A.L.; Haucke, V. Phosphatidylinositol 3-phosphates-at the interface between cell signalling and membrane traffic. EMBO J., 2016, 35(6), 561-579.
[http://dx.doi.org/10.15252/embj.201593564] [PMID: 26888746]
[15]
De Craene, J-O.; Bertazzi, D.L.; Bär, S.; Friant, S. Phosphoinositides, major actors in membrane trafficking and lipid signaling pathways. Int. J. Mol. Sci., 2017, 18(3), 634.
[http://dx.doi.org/10.3390/ijms18030634] [PMID: 28294977]
[16]
Hiles, I.D.; Otsu, M.; Volinia, S.; Fry, M.J.; Gout, I.; Dhand, R.; Panayotou, G.; Ruiz-Larrea, F.; Thompson, A.; Totty, N.F. Phosphatidylinositol 3-kinase: structure and expression of the 110 kd catalytic subunit. Cell, 1992, 70(3), 419-429 Available at.http://www.ncbi.nlm.nih.gov/pubmed/1322797(Accessed April 3, 2018).
[http://dx.doi.org/10.1016/0092-8674(92)90166-A] [PMID: 1322797]
[17]
Martin, T.F.J. Phosphoinositide lipids as signaling molecules: common themes for signal transduction, cytoskeletal regulation, and membrane trafficking. Annu. Rev. Cell Dev. Biol., 1998, 14, 231-264.
[http://dx.doi.org/10.1146/annurev.cellbio.14.1.231] [PMID: 9891784]
[18]
Fruman, D.A.; Meyers, R.E.; Cantley, L.C. Phosphoinositide kinases. Annu. Rev. Biochem., 1998, 67, 481-507.
[http://dx.doi.org/10.1146/annurev.biochem.67.1.481] [PMID: 9759495]
[19]
Vanhaesebroeck, B.; Waterfield, M.D. Signaling by distinct classes of phosphoinositide 3-kinases. Exp. Cell Res., 1999, 253(1), 239-254.
[http://dx.doi.org/10.1006/excr.1999.4701] [PMID: 10579926]
[20]
Brown, R.A.; Shepherd, P.R. Growth factor regulation of the novel class II phosphoinositide 3-kinases. Biochem. Soc. Trans., 2001, 29, (Pt 4), 535-537. Acailable at.http://www.ncbi.nlm.nih.gov/pubmed/11498023(Accessed April 3, 2018)..
[http://dx.doi.org/10.1042/bst0290535] [PMID: 11498023]
[21]
Gaidarov, I.; Smith, M.E.; Domin, J.; Keen, J.H. The class II phosphoinositide 3-kinase C2alpha is activated by clathrin and regulates clathrin-mediated membrane trafficking. Mol. Cell, 2001, 7(2), 443-449 Available at.http://www.ncbi.nlm.nih.gov/pubmed/11239472(Accessed April 3, 2018)..
[http://dx.doi.org/10.1016/S1097-2765(01)00191-5] [PMID: 11239472]
[22]
Kihara, A.; Noda, T.; Ishihara, N.; Ohsumi, Y. Two distinct Vps34 phosphatidylinositol 3-kinase complexes function in autophagy and carboxypeptidase Y sorting in Saccharomyces cerevisiae. J. Cell Biol., 2001, 152(3), 519-530 Available at.http://www.ncbi.nlm.nih.gov/pubmed/11157979(Accessed April 3, 2018)..
[http://dx.doi.org/10.1083/jcb.152.3.519] [PMID: 11157979]
[23]
Hall, B.S.; Gabernet-Castello, C.; Voak, A.; Goulding, D.; Natesan, S.K.; Field, M.C. TbVps34, the trypanosome orthologue of Vps34, is required for Golgi complex segregation. J. Biol. Chem., 2006, 281(37), 27600-27612.
[http://dx.doi.org/10.1074/jbc.M602183200] [PMID: 16835237]
[24]
Schoijet, A.C.; Miranda, K.; Girard-Dias, W.; de Souza, W.; Flawiá, M.M.; Torres, H.N.; Docampo, R.; Alonso, G.D. A Trypanosoma cruzi phosphatidylinositol 3-kinase (TcVps34) is involved in osmoregulation and receptor-mediated endocytosis. J. Biol. Chem., 2008, 283(46), 31541-31550.
[http://dx.doi.org/10.1074/jbc.M801367200] [PMID: 18801733]
[25]
Schoijet, A.C.; Miranda, K.; Sternlieb, T.; Barrera, N.M.; Girard-Dias, W.; de Souza, W.; Alonso, G.D. TbVps15 is required for vesicular transport and cytokinesis in Trypanosoma brucei. Mol. Biochem. Parasitol., 2018, 219, 33-41.
[http://dx.doi.org/10.1016/j.molbiopara.2017.11.004] [PMID: 29155083]
[26]
Gimenez, A.M.; Gesumaría, M.C.; Schoijet, A.C.; Alonso, G.D.; Flawiá, M.M.; Racagni, G.E.; Machado, E.E. Phosphatidylinositol kinase activities in Trypanosoma cruzi epimastigotes. Mol. Biochem. Parasitol., 2015, 203(1-2), 14-24.
[http://dx.doi.org/10.1016/j.molbiopara.2015.10.002] [PMID: 26493613]
[27]
Minning, T.A.; Weatherly, D.B.; Atwood, J., III; Orlando, R.; Tarleton, R.L. The steady-state transcriptome of the four major life-cycle stages of Trypanosoma cruzi. BMC Genomics, 2009, 10, 370.
[http://dx.doi.org/10.1186/1471-2164-10-370] [PMID: 19664227]
[28]
Berridge, M.J.; Lipp, P.; Bootman, M.D. 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]
[29]
Clapham, D.E. Calcium signaling. Cell, 2007, 131(6), 1047-1058.
[http://dx.doi.org/10.1016/j.cell.2007.11.028] [PMID: 18083096]
[30]
Cai, X. Subunit stoichiometry and channel pore structure of ion channels: all for one, or one for one? J. Physiol., 2008, 586(4), 925-926.
[http://dx.doi.org/10.1113/jphysiol.2007.149153] [PMID: 18079155]
[31]
Luzio, J.P.; Gray, S.R.; Bright, N.A. Endosome-lysosome fusion. Biochem. Soc. Trans., 2010, 38(6), 1413-1416.
[http://dx.doi.org/10.1042/BST0381413] [PMID: 21118098]
[32]
Christensen, K.A.; Myers, J.T.; Swanson, J.A. pH-dependent regulation of lysosomal calcium in macrophages. J. Cell Sci., 2002, 115(Pt 3), 599-607 Available at.http://www.ncbi.nlm.nih.gov/pubmed/11861766(Accessed July 17, 2019)..
[PMID: 11861766]
[33]
Hay, J.C. Calcium: a fundamental regulator of intracellular membrane fusion? EMBO Rep., 2007, 8(3), 236-240.
[http://dx.doi.org/10.1038/sj.embor.7400921] [PMID: 17330068]
[34]
Sherwood, M.W.; Prior, I.A.; Voronina, S.G.; Barrow, S.L.; Woodsmith, J.D.; Gerasimenko, O.V.; Petersen, O.H.; Tepikin, A.V. Activation of trypsinogen in large endocytic vacuoles of pancreatic acinar cells. Proc. Natl. Acad. Sci. USA, 2007, 104(13), 5674-5679.
[http://dx.doi.org/10.1073/pnas.0700951104] [PMID: 17363470]
[35]
Zampese, E.; Pizzo, P. Intracellular organelles in the saga of Ca2+ homeostasis: different molecules for different purposes? Cell. Mol. Life Sci., 2012, 69(7), 1077-1104.
[http://dx.doi.org/10.1007/s00018-011-0845-9] [PMID: 21968921]
[36]
Docampo, R.; Scott, D.A.; Vercesi, A.E.; Moreno, S.N. Intracellular Ca2+ storage in acidocalcisomes of Trypanosoma cruzi. Biochem. J., 1995, 310(Pt 3), 1005-1012 Available at.http://www.ncbi.nlm.nih.gov/pubmed/7575396(Accessed March 19, 2018)..
[http://dx.doi.org/10.1042/bj3101005] [PMID: 7575396]
[37]
Vercesi, A.E.; Moreno, S.N.; Docampo, R. Ca2+/H+ exchange in acidic vacuoles of Trypanosoma brucei. Biochem. J., 1994, 304(Pt 1), 227-233 Available at.http://www.ncbi.nlm.nih.gov/pubmed/7998937(Accessed March 19, 2018)..
[http://dx.doi.org/10.1042/bj3040227] [PMID: 7998937]
[38]
Docampo, R.; de Souza, W.; Miranda, K.; Rohloff, P.; Moreno, S.N.J. Acidocalcisomes - conserved from bacteria to man. Nat. Rev. Microbiol., 2005, 3(3), 251-261.
[http://dx.doi.org/10.1038/nrmicro1097] [PMID: 15738951]
[39]
Docampo, R.; Moreno, S.N.J. Acidocalcisomes. Cell Calcium, 2011, 50(2), 113-119.
[http://dx.doi.org/10.1016/j.ceca.2011.05.012] [PMID: 21752464]
[40]
Patel, S.; Docampo, R. Acidic calcium stores open for business: expanding the potential for intracellular Ca2+ signaling. Trends Cell Biol., 2010, 20(5), 277-286.
[http://dx.doi.org/10.1016/j.tcb.2010.02.003] [PMID: 20303271]
[41]
Hashimoto, M.; Enomoto, M.; Morales, J.; Kurebayashi, N.; Sakurai, T.; Hashimoto, T.; Nara, T.; Mikoshiba, K. Inositol 1,4,5-trisphosphate receptor regulates replication, differentiation, infectivity and virulence of the parasitic protist Trypanosoma cruzi. Mol. Microbiol., 2013, 87(6), 1133-1150.
[http://dx.doi.org/10.1111/mmi.12155] [PMID: 23320762]
[42]
Ulrich, P.N.; Jimenez, V.; Park, M.; Martins, V.P.; Atwood, J., III; Moles, K.; Collins, D.; Rohloff, P.; Tarleton, R.; Moreno, S.N.J.; Orlando, R.; Docampo, R. Identification of contractile vacuole proteins in Trypanosoma cruzi. PLoS One, 2011, 6(3)e18013
[http://dx.doi.org/10.1371/journal.pone.0018013] [PMID: 21437209]
[43]
Huang, G.; Bartlett, P.J.; Thomas, A.P.; Moreno, S.N.J.; Docampo, R. Acidocalcisomes of Trypanosoma brucei have an inositol 1,4,5-trisphosphate receptor that is required for growth and infectivity. Proc. Natl. Acad. Sci. USA, 2013, 110(5), 1887-1892.
[http://dx.doi.org/10.1073/pnas.1216955110] [PMID: 23319604]
[44]
Prole, D.L.; Taylor, C.W. Identification of intracellular and plasma membrane calcium channel homologues in pathogenic parasites. PLoS One, 2011, 6(10)e26218
[http://dx.doi.org/10.1371/journal.pone.0026218] [PMID: 22022573]
[45]
Ríos, E. The cell boundary theorem: a simple law of the control of cytosolic calcium concentration. J. Physiol. Sci., 2010, 60(1), 81-84.
[http://dx.doi.org/10.1007/s12576-009-0069-z] [PMID: 19937486]
[46]
Lu, H.G.; Zhong, L.; de Souza, W.; Benchimol, M.; Moreno, S.; Docampo, R. Ca2+ content and expression of an acidocalcisomal calcium pump are elevated in intracellular forms of Trypanosoma cruzi. Mol. Cell. Biol., 1998, 18(4), 2309-2323.
[http://dx.doi.org/10.1128/MCB.18.4.2309] [PMID: 9528801]
[47]
Benaim, G.; Losada, S.; Gadelha, F.R.; Docampo, R. A calmodulin-activated (Ca(2+)-Mg2+)-ATPase is involved in Ca2+ transport by plasma membrane vesicles from Trypanosoma cruzi. Biochem. J., 1991, 280(Pt 3), 715-720 Available at.http://www.ncbi.nlm.nih.gov/pubmed/1837215(Accessed March 20, 2018)..
[http://dx.doi.org/10.1042/bj2800715] [PMID: 1837215]
[48]
Téllez-Iñón, M.T.; Ulloa, R.M.; Torruella, M.; Torres, H.N. Calmodulin and Ca2+-dependent cyclic AMP phosphodiesterase activity in Trypanosoma cruzi. Mol. Biochem. Parasitol., 1985, 17(2), 143-153 Available at.http://www.ncbi.nlm.nih.gov/pubmed/2999589(Accessed March 20, 201)..
[http://dx.doi.org/10.1016/0166-6851(85)90013-1] [PMID: 2999589]
[49]
Garcia-Marchan, Y.; Sojo, F.; Rodriguez, E.; Zerpa, N.; Malave, C.; Galindo-Castro, I.; Salerno, M.; Benaim, G. Trypanosoma cruzi calmodulin: cloning, expression and characterization. Exp. Parasitol., 2009, 123(4), 326-333.
[http://dx.doi.org/10.1016/j.exppara.2009.08.010] [PMID: 19703447]
[50]
Ginger, M.L.; Collingridge, P.W.; Brown, R.W.B.; Sproat, R.; Shaw, M.K.; Gull, K. Calmodulin is required for paraflagellar rod assembly and flagellum-cell body attachment in trypanosomes. Protist, 2013, 164(4), 528-540.
[http://dx.doi.org/10.1016/j.protis.2013.05.002] [PMID: 23787017]
[51]
Engman, D.M.; Krause, K.H.; Blumin, J.H.; Kim, K.S.; Kirchhoff, L.V.; Donelson, J.E. A novel flagellar Ca2+-binding protein in trypanosomes. J. Biol. Chem., 1989, 264(31), 18627-18631 Available at.http://www.ncbi.nlm.nih.gov/pubmed/2681200(Accessed March 26, 2018)..
[PMID: 2681200]
[52]
Wu, Y.; Deford, J.; Benjamin, R.; Lee, M.G.; Ruben, L. The gene family of EF-hand calcium-binding proteins from the flagellum of Trypanosoma brucei. Biochem. J., 1994, 304(Pt 3), 833-841 Available at.http://www.ncbi.nlm.nih.gov/pubmed/7818488(Accessed March 26, 2018)..
[http://dx.doi.org/10.1042/bj3040833] [PMID: 7818488]
[53]
Furuya, T.; Kashuba, C.; Docampo, R.; Moreno, S.N. A novel phosphatidylinositol-phospholipase C of Trypanosoma cruzi that is lipid modified and activated during trypomastigote to amastigote differentiation. J. Biol. Chem., 2000, 275(9), 6428-6438 Available at.http://www.ncbi.nlm.nih.gov/pubmed/10692446(Accessed March 26, 2018)..
[http://dx.doi.org/10.1074/jbc.275.9.6428] [PMID: 10692446]
[54]
Docampo, R.; Lukeš, J. Trypanosomes and the solution to a 50-year mitochondrial calcium mystery. Trends Parasitol., 2012, 28(1), 31-37.
[http://dx.doi.org/10.1016/j.pt.2011.10.007] [PMID: 22088944]
[55]
Huang, G.; Vercesi, A.E.; Docampo, R. Essential regulation of cell bioenergetics in Trypanosoma brucei by the mitochondrial calcium uniporter. Nat. Commun., 2013, 4, 2865.
[http://dx.doi.org/10.1038/ncomms3865] [PMID: 24305511]
[56]
Lucas, K.A.; Pitari, G.M.; Kazerounian, S.; Ruiz-Stewart, I.; Park, J.; Schulz, S.; Chepenik, K.P.; Waldman, S.A. Guanylyl cyclases and signaling by cyclic GMP. Pharmacol. Rev., 2000, 52(3), 375-414 Available at.http://www.ncbi.nlm.nih.gov/pubmed/10977868(Accessed March 1, 2018)..
[PMID: 10977868]
[57]
Seebeck, T.; Gong, K.; Kunz, S.; Schaub, R.; Shalaby, T.; Zoraghi, R. cAMP signalling in Trypanosoma brucei. Int. J. Parasitol., 2001, 31(5-6), 491-498 Available at.http://www.ncbi.nlm.nih.gov/pubmed/11334934(Accessed March 1, 2018)..
[http://dx.doi.org/10.1016/S0020-7519(01)00164-3] [PMID: 11334934]
[58]
Laxman, S.; Beavo, J.A. Cyclic nucleotide signaling mechanisms in trypanosomes: possible targets for therapeutic agents. Mol. Interv., 2007, 7(4), 203-215.
[http://dx.doi.org/10.1124/mi.7.4.7] [PMID: 17827441]
[59]
Rangel-Aldao, R.; Allende, O.; Triana, F.; Piras, R.; Henriquez, D.; Piras, M. Possible role of cAMP in the differentiation of Trypanosoma cruzi. Mol. Biochem. Parasitol., 1987, 22(1), 39-43 Available at.http://www.ncbi.nlm.nih.gov/pubmed/3027556(Accessed March 1, 2018)..
[http://dx.doi.org/10.1016/0166-6851(87)90067-3] [PMID: 3027556]
[60]
Flawiá, M.M.; Téllez-Iñón, M.T.; Torres, H.N. Signal transduction mechanisms in Trypanosoma cruzi. Parasitol. Today (Regul. Ed.), 1987, 13(1), 30-33. Available at.http://www.ncbi.nlm.nih.gov/pubmed/15275164(Accessed March 1, 2018)..
[http://dx.doi.org/10.1016/S0169-4758(96)10070-3] [PMID: 15275164]
[61]
Pays, E.; Tebabi, P.; Pays, A.; Coquelet, H.; Revelard, P.; Salmon, D.; Steinert, M. The genes and transcripts of an antigen gene expression site from T. brucei. Cell, 1989, 57(5), 835-845 Available at.http://www.ncbi.nlm.nih.gov/pubmed/2720787(Accessed March 14, 2018)..
[http://dx.doi.org/10.1016/0092-8674(89)90798-8] [PMID: 2720787]
[62]
Paindavoine, P.; Rolin, S.; Van Assel, S.; Geuskens, M.; Jauniaux, J.C.; Dinsart, C.; Huet, G.; Pays, E. A gene from the variant surface glycoprotein expression site encodes one of several transmembrane adenylate cyclases located on the flagellum of Trypanosoma brucei. Mol. Cell. Biol., 1992, 12(3), 1218-1225 Available at.http://www.ncbi.nlm.nih.gov/pubmed/1545803(Accessed March 14, 2018)..
[http://dx.doi.org/10.1128/MCB.12.3.1218] [PMID: 1545803]
[63]
Salmon, D.; Vanwalleghem, G.; Morias, Y.; Denoeud, J.; Krumbholz, C.; Lhomme, F.; Bachmaier, S.; Kador, M.; Gossmann, J.; Dias, F.B.S.; De Muylder, G.; Uzureau, P.; Magez, S.; Moser, M.; De Baetselier, P.; Van Den Abbeele, J.; Beschin, A.; Boshart, M.; Pays, E. Adenylate cyclases of trypanosoma brucei inhibit the innate immune response of the host. Science, 2012, 337(6093), 463-466.
[http://dx.doi.org/10.1126/science.1222753] [PMID: 22700656]
[64]
Alexandre, S.; Paindavoine, P.; Tebabi, P.; Pays, A.; Halleux, S.; Steinert, M.; Pays, E. Differential expression of a family of putative adenylate/guanylate cyclase genes in Trypanosoma brucei. Mol. Biochem. Parasitol., 1990, 43(2), 279-288 Available at.http://www.ncbi.nlm.nih.gov/pubmed/1982555(Accessed March 14, 2018)..
[http://dx.doi.org/10.1016/0166-6851(90)90152-C] [PMID: 1982555]
[65]
Alexandre, S.; Paindavoine, P.; Hanocq-Quertier, J.; Paturiaux-Hanocq, F.; Tebabi, P.; Pays, E. Families of adenylate cyclase genes in Trypanosoma brucei. Mol. Biochem. Parasitol., 1996, 77(2), 173-182. Available at.http://www.ncbi.nlm.nih.gov/pubmed/8813663(Accessed March 15, 2018).
[http://dx.doi.org/10.1016/0166-6851(96)02591-1] [PMID: 8813663]
[66]
Rolin, S.; Paindavoine, P.; Hanocq-Quertier, J.; Hanocq, F.; Claes, Y.; Le Ray, D.; Overath, P.; Pays, E. Transient adenylate cyclase activation accompanies differentiation of Trypanosoma brucei from bloodstream to procyclic forms. Mol. Biochem. Parasitol., 1993, 61(1), 115-125 Available at.http://www.ncbi.nlm.nih.gov/pubmed/8259124(Accessed March 15, 2018)..
[http://dx.doi.org/10.1016/0166-6851(93)90164-S] [PMID: 8259124]
[67]
Naula, C.; Schaub, R.; Leech, V.; Melville, S.; Seebeck, T. Spontaneous dimerization and leucine-zipper induced activation of the recombinant catalytic domain of a new adenylyl cyclase of Trypanosoma brucei, GRESAG4.4B. Mol. Biochem. Parasitol., 2001, 112(1), 19-28 Available at.http://www.ncbi.nlm.nih.gov/pubmed/11166383(Accessed March 15, 2018)..
[http://dx.doi.org/10.1016/S0166-6851(00)00338-8] [PMID: 11166383]
[68]
Salmon, D.; Bachmaier, S.; Krumbholz, C.; Kador, M.; Gossmann, J.A.; Uzureau, P.; Pays, E.; Boshart, M. Cytokinesis of Trypanosoma brucei bloodstream forms depends on expression of adenylyl cyclases of the ESAG4 or ESAG4-like subfamily. Mol. Microbiol., 2012, 84(2), 225-242.
[http://dx.doi.org/10.1111/j.1365-2958.2012.08013.x] [PMID: 22340731]
[69]
Oberholzer, M.; Lopez, M.A.; McLelland, B.T.; Hill, K.L. Social motility in african trypanosomes. PLoS Pathog., 2010, 6(1)e1000739
[http://dx.doi.org/10.1371/journal.ppat.1000739] [PMID: 20126443]
[70]
Lopez, M.A.; Saada, E.A.; Hill, K.L. Insect stage-specific adenylate cyclases regulate social motility in African trypanosomes. Eukaryot. Cell, 2015, 14(1), 104-112.
[http://dx.doi.org/10.1128/EC.00217-14] [PMID: 25416239]
[71]
Huang, H.; Werner, C.; Weiss, L.M.; Wittner, M.; Orr, G.A. Molecular cloning and expression of the catalytic subunit of protein kinase A from Trypanosoma cruzi. Int. J. Parasitol., 2002, 32(9), 1107-1115 Available at.http://www.ncbi.nlm.nih.gov/pubmed/12117493(Accessed March 1, 2018)..
[http://dx.doi.org/10.1016/S0020-7519(02)00085-1] [PMID: 12117493]
[72]
Huang, H.; Weiss, L.M.; Nagajyothi, F.; Tanowitz, H.B.; Wittner, M.; Orr, G.A.; Bao, Y. Molecular cloning and characterization of the protein kinase A regulatory subunit of Trypanosoma cruzi. Mol. Biochem. Parasitol., 2006, 149(2), 242-245.
[http://dx.doi.org/10.1016/j.molbiopara.2006.05.008] [PMID: 16815565]
[73]
Bao, Y.; Weiss, L.M.; Braunstein, V.L.; Huang, H. Role of protein kinase A in Trypanosoma cruzi. Infect. Immun., 2008, 76(10), 4757-4763.
[http://dx.doi.org/10.1128/IAI.00527-08] [PMID: 18694966]
[74]
Bao, Y.; Weiss, L.M.; Ma, Y.F.; Kahn, S.; Huang, H. Protein kinase A catalytic subunit interacts and phosphorylates members of trans-sialidase super-family in Trypanosoma cruzi. Microbes Infect., 2010, 12(10), 716-726.
[http://dx.doi.org/10.1016/j.micinf.2010.04.014] [PMID: 20466066]
[75]
Shalaby, T.; Liniger, M.; Seebeck, T. The regulatory subunit of a cGMP-regulated protein kinase A of Trypanosoma brucei. Eur. J. Biochem., 2001, 268(23), 6197-6206 Available at.http://www.ncbi.nlm.nih.gov/pubmed/11733015(Accessed March 13, 2018)..
[http://dx.doi.org/10.1046/j.0014-2956.2001.02564.x] [PMID: 11733015]
[76]
Siman-Tov, M.M.; Aly, R.; Shapira, M.; Jaffe, C.L. Cloning from Leishmania major of a developmentally regulated gene, c-lpk2, for the catalytic subunit of the cAMP-dependent protein kinase. Mol. Biochem. Parasitol., 1996, 77(2), 201-215 Available at.http://www.ncbi.nlm.nih.gov/pubmed/8813666(Accessed March 13, 2018)..
[http://dx.doi.org/10.1016/0166-6851(96)02601-1] [PMID: 8813666]
[77]
Siman-Tov, M.M.; Ivens, A.C.; Jaffe, C.L. Molecular cloning and characterization of two new isoforms of the protein kinase A catalytic subunit from the human parasite Leishmania. Gene, 2002, 288(1-2), 65-75 Available at.http://www.ncbi.nlm.nih.gov/pubmed/12034495(Accessed March 13, 2018)..
[http://dx.doi.org/10.1016/S0378-1119(02)00403-1] [PMID: 12034495]
[78]
Bhattacharya, A.; Biswas, A.; Das, P.K. Identification of a protein kinase A regulatory subunit from Leishmania having importance in metacyclogenesis through induction of autophagy. Mol. Microbiol., 2012, 83(3), 548-564.
[http://dx.doi.org/10.1111/j.1365-2958.2011.07950.x] [PMID: 22168343]
[79]
Jäger, A.V.; De Gaudenzi, J.G.; Mild, J.G.; Mc Cormack, B.; Pantano, S.; Altschuler, D.L.; Edreira, M.M. Identification of novel cyclic nucleotide binding proteins in Trypanosoma cruzi. Mol. Biochem. Parasitol., 2014, 198(2), 104-112.
[http://dx.doi.org/10.1016/j.molbiopara.2015.02.002] [PMID: 25724722]
[80]
Gould, M.K.; Bachmaier, S.; Ali, J.A.M.; Alsford, S.; Tagoe, D.N.A.; Munday, J.C.; Schnaufer, A.C.; Horn, D.; Boshart, M.; de Koning, H.P. Cyclic AMP effectors in African trypanosomes revealed by genome-scale RNA interference library screening for resistance to the phosphodiesterase inhibitor CpdA. Antimicrob. Agents Chemother., 2013, 57(10), 4882-4893.
[http://dx.doi.org/10.1128/AAC.00508-13] [PMID: 23877697]
[81]
Conti, M. Phosphodiesterases and cyclic nucleotide signaling in endocrine cells. Mol. Endocrinol., 2000, 14(9), 1317-1327.
[http://dx.doi.org/10.1210/mend.14.9.0534] [PMID: 10976911]
[82]
Lefkowitz, R.J. Historical review: a brief history and personal retrospective of seven-transmembrane receptors. Trends Pharmacol. Sci., 2004, 25(8), 413-422.
[http://dx.doi.org/10.1016/j.tips.2004.06.006] [PMID: 15276710]
[83]
Houslay, M.D.; Adams, D.R. PDE4 cAMP phosphodiesterases: modular enzymes that orchestrate signalling cross-talk, desensitization and compartmentalization. Biochem. J., 2003, 370(Pt 1), 1-18.
[http://dx.doi.org/10.1042/bj20021698] [PMID: 12444918]
[84]
Houslay, M.D. Underpinning compartmentalised cAMP signalling through targeted cAMP breakdown. Trends Biochem. Sci., 2010, 35(2), 91-100.
[http://dx.doi.org/10.1016/j.tibs.2009.09.007] [PMID: 19864144]
[85]
Conti, M.; Mika, D.; Richter, W. Cyclic AMP compartments and signaling specificity: role of cyclic nucleotide phosphodiesterases. J. Gen. Physiol., 2014, 143(1), 29-38.
[http://dx.doi.org/10.1085/jgp.201311083] [PMID: 24378905]
[86]
Maurice, D.H.; Ke, H.; Ahmad, F.; Wang, Y.; Chung, J.; Manganiello, V.C. Advances in targeting cyclic nucleotide phosphodiesterases. Nat. Rev. Drug Discov., 2014, 13(4), 290-314.
[http://dx.doi.org/10.1038/nrd4228] [PMID: 24687066]
[87]
Beavo, J.A. Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms. Physiol. Rev., 1995, 75(4), 725-748.
[http://dx.doi.org/10.1152/physrev.1995.75.4.725] [PMID: 7480160]
[88]
Keravis, T.; Lugnier, C. Cyclic nucleotide phosphodiesterases (PDE) and peptide motifs. Curr. Pharm. Des., 2010, 16(9), 1114-1125 Available at.http://www.ncbi.nlm.nih.gov/pubmed/20030615(Accessed March 6, 2018)..
[http://dx.doi.org/10.2174/138161210790963760] [PMID: 20030615]
[89]
Francis, S.H.; Blount, M.A.; Corbin, J.D. Mammalian cyclic nucleotide phosphodiesterases: molecular mechanisms and physiological functions. Physiol. Rev., 2011, 91(2), 651-690.
[http://dx.doi.org/10.1152/physrev.00030.2010] [PMID: 21527734]
[90]
Conti, M.; Beavo, J. Biochemistry and physiology of cyclic nucleotide phosphodiesterases: essential components in cyclic nucleotide signaling. Annu. Rev. Biochem., 2007, 76, 481-511.
[http://dx.doi.org/10.1146/annurev.biochem.76.060305.150444] [PMID: 17376027]
[91]
Thompson, W.J. Cyclic nucleotide phosphodiesterases: pharmacology, biochemistry and function. Pharmacol. Ther., 1991, 51(1), 13-33 Available at.http://www.ncbi.nlm.nih.gov/pubmed/1663250(Accessed February 19, 2019)..
[http://dx.doi.org/10.1016/0163-7258(91)90039-O] [PMID: 1663250]
[92]
Bolger, G.B. Molecular biology of the cyclic AMP-specific cyclic nucleotide phosphodiesterases: a diverse family of regulatory enzymes. Cell. Signal., 1994, 6(8), 851-859 Available at.http://www.ncbi.nlm.nih.gov/pubmed/7718405(Accessed February 19, 2019)..
[http://dx.doi.org/10.1016/0898-6568(94)90018-3] [PMID: 7718405]
[93]
Bender, A.T.; Beavo, J.A. Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. Pharmacol. Rev., 2006, 58(3), 488-520.
[http://dx.doi.org/10.1124/pr.58.3.5] [PMID: 16968949]
[94]
Gancedo, J.M. Biological roles of cAMP: variations on a theme in the different kingdoms of life. Biol. Rev. Camb. Philos. Soc., 2013, 88(3), 645-668.
[http://dx.doi.org/10.1111/brv.12020] [PMID: 23356492]
[95]
Keravis, T.; Lugnier, C. Cyclic nucleotide phosphodiesterase (PDE) isozymes as targets of the intracellular signalling network: benefits of PDE inhibitors in various diseases and perspectives for future therapeutic developments. Br. J. Pharmacol., 2012, 165(5), 1288-1305.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01729.x] [PMID: 22014080]
[96]
Vij, A.; Biswas, A.; Bhattacharya, A.; Das, P.K. A soluble phosphodiesterase in Leishmania donovani negatively regulates cAMP signaling by inhibiting protein kinase A through a two way process involving catalytic as well as non-catalytic sites. Int. J. Biochem. Cell Biol., 2014, 57, 197-206.
[http://dx.doi.org/10.1016/j.biocel.2014.10.003] [PMID: 25310904]
[97]
D’Angelo, M.A.; Sanguineti, S.; Reece, J.M.; Birnbaumer, L.; Torres, H.N.; Flawiá, M.M. Identification, characterization and subcellular localization of TcPDE1, a novel cAMP-specific phosphodiesterase from Trypanosoma cruzi. Biochem. J., 2004, 378(Pt 1), 63-72.
[http://dx.doi.org/10.1042/bj20031147] [PMID: 14556647]
[98]
Díaz-Benjumea, R.; Laxman, S.; Hinds, T.R.; Beavo, J.A.; Rascón, A. Characterization of a novel cAMP-binding, cAMP-specific cyclic nucleotide phosphodiesterase (TcrPDEB1) from Trypanosoma cruzi. Biochem. J., 2006, 399(2), 305-314.
[http://dx.doi.org/10.1042/BJ20060757] [PMID: 16776650]
[99]
Alonso, G.D.; Schoijet, A.C.; Torres, H.N.; Flawiá, M.M. TcrPDEA1, a cAMP-specific phosphodiesterase with atypical pharmacological properties from Trypanosoma cruzi. Mol. Biochem. Parasitol., 2007, 152(1), 72-79.
[http://dx.doi.org/10.1016/j.molbiopara.2006.12.002] [PMID: 17222469]
[100]
Alonso, G.D.; Schoijet, A.C.; Torres, H.N.; Flawiá, M.M. TcPDE4, a novel membrane-associated cAMP-specific phosphodiesterase from Trypanosoma cruzi. Mol. Biochem. Parasitol., 2006, 145(1), 40-49.
[http://dx.doi.org/10.1016/j.molbiopara.2005.09.005] [PMID: 16225937]
[101]
Kunz, S.; Oberholzer, M.; Seebeck, T. A FYVE-containing unusual cyclic nucleotide phosphodiesterase from Trypanosoma cruzi. FEBS J., 2005, 272(24), 6412-6422.
[http://dx.doi.org/10.1111/j.1742-4658.2005.05039.x] [PMID: 16336277]
[102]
Schoijet, A.C.; Miranda, K.; Medeiros, L.C.S.; de Souza, W.; Flawiá, M.M.; Torres, H.N.; Pignataro, O.P.; Docampo, R.; Alonso, G.D. Defining the role of a FYVE domain in the localization and activity of a cAMP phosphodiesterase implicated in osmoregulation in Trypanosoma cruzi. Mol. Microbiol., 2011, 79(1), 50-62.
[http://dx.doi.org/10.1111/j.1365-2958.2010.07429.x] [PMID: 21166893]
[103]
Oberholzer, M.; Marti, G.; Baresic, M.; Kunz, S.; Hemphill, A.; Seebeck, T. The Trypanosoma brucei cAMP phosphodiesterases TbrPDEB1 and TbrPDEB2: flagellar enzymes that are essential for parasite virulence. FASEB J., 2007, 21(3), 720-731.
[http://dx.doi.org/10.1096/fj.06-6818com] [PMID: 17167070]
[104]
Portman, N.; Gull, K. The paraflagellar rod of kinetoplastid parasites: from structure to components and function. Int. J. Parasitol., 2010, 40(2), 135-148.
[http://dx.doi.org/10.1016/j.ijpara.2009.10.005] [PMID: 19879876]
[105]
Oberholzer, M.; Saada, E.A.; Hill, K.L. Cyclic AMP regulates social behavior in african trypanosomes. MBio, 2015, 6(3), e01954-e14.
[http://dx.doi.org/10.1128/mBio.01954-14] [PMID: 25922395]
[106]
Rohloff, P.; Docampo, R. A contractile vacuole complex is involved in osmoregulation in Trypanosoma cruzi. Exp. Parasitol., 2008, 118(1), 17-24.
[http://dx.doi.org/10.1016/j.exppara.2007.04.013] [PMID: 17574552]
[107]
Bhattacharya, A.; Biswas, A.; Das, P.K. Role of a differentially expressed cAMP phosphodiesterase in regulating the induction of resistance against oxidative damage in Leishmania donovani. Free Radic. Biol. Med., 2009, 47(10), 1494-1506.
[http://dx.doi.org/10.1016/j.freeradbiomed.2009.08.025] [PMID: 19733234]
[108]
Biswas, A.; Bhattacharya, A.; Das, P.K. Role of cAMP signaling in the survival and infectivity of the protozoan parasite, leishmania donovani. Mol. Biol. Int., 2011, 2011782971
[http://dx.doi.org/10.4061/2011/782971] [PMID: 22091412]
[109]
de Koning, H.P.; Gould, M.K.; Sterk, G.J.; Tenor, H.; Kunz, S.; Luginbuehl, E.; Seebeck, T. Pharmacological validation of Trypanosoma brucei phosphodiesterases as novel drug targets. J. Infect. Dis., 2012, 206(2), 229-237.
[http://dx.doi.org/10.1093/infdis/jir857] [PMID: 22291195]
[110]
King-Keller, S.; Li, M.; Smith, A.; Zheng, S.; Kaur, G.; Yang, X.; Wang, B.; Docampo, R. Chemical validation of phosphodiesterase C as a chemotherapeutic target in Trypanosoma cruzi, the etiological agent of Chagas’ disease. Antimicrob. Agents Chemother., 2010, 54(9), 3738-3745.
[http://dx.doi.org/10.1128/AAC.00313-10] [PMID: 20625148]
[111]
Wang, H.; Kunz, S.; Chen, G.; Seebeck, T.; Wan, Y.; Robinson, H.; Martinelli, S.; Ke, H. Biological and structural characterization of Trypanosoma cruzi phosphodiesterase C and implications for design of parasite selective inhibitors. J. Biol. Chem., 2012, 287(15), 11788-11797.
[http://dx.doi.org/10.1074/jbc.M111.326777] [PMID: 22356915]
[112]
Jansen, C.; Wang, H.; Kooistra, A.J.; de Graaf, C.; Orrling, K.M.; Tenor, H.; Seebeck, T.; Bailey, D.; de Esch, I.J.P.; Ke, H.; Leurs, R. Discovery of novel Trypanosoma brucei phosphodiesterase B1 inhibitors by virtual screening against the unliganded TbrPDEB1 crystal structure. J. Med. Chem., 2013, 56(5), 2087-2096.
[http://dx.doi.org/10.1021/jm3017877] [PMID: 23409953]
[113]
Wang, H.; Yan, Z.; Geng, J.; Kunz, S.; Seebeck, T.; Ke, H. Crystal structure of the Leishmania major phosphodiesterase LmjPDEB1 and insight into the design of the parasite-selective inhibitors. Mol. Microbiol., 2007, 66(4), 1029-1038.
[http://dx.doi.org/10.1111/j.1365-2958.2007.05976.x] [PMID: 17944832]
[114]
Aguilera, E.; Alvarez, G.; Cerecetto, H.; Gonzalez, M. Polypharmacology in the treatment of chagas disease. Curr. Med. Chem., 2018, 25.
[http://dx.doi.org/10.2174/0929867325666180410101728] [PMID: 29637852]
[115]
Aguilera, E.; Varela, J.; Serna, E.; Torres, S.; Yaluff, G.; Bilbao, N.V.; Cerecetto, H.; Alvarez, G.; González, M. Looking for combination of benznidazole and Trypanosoma cruzi-triosephosphate isomerase inhibitors for Chagas disease treatment. Mem. Inst. Oswaldo Cruz, 2018, 113(3), 153-160.
[http://dx.doi.org/10.1590/0074-02760170267] [PMID: 29412353]
[116]
Dichiara, M.; Marrazzo, A.; Prezzavento, O.; Collina, S.; Rescifina, A.; Amata, E. Repurposing of human kinase inhibitors in neglected protozoan diseases. ChemMedChem, 2017, 12(16), 1235-1253.
[http://dx.doi.org/10.1002/cmdc.201700259] [PMID: 28590590]
[117]
Lara-Ramirez, E.E.; López-Cedillo, J.C.; Nogueda-Torres, B.; Kashif, M.; Garcia-Perez, C.; Bocanegra-Garcia, V.; Agusti, R.; Uhrig, M.L.; Rivera, G. An in vitro and in vivo evaluation of new potential trans-sialidase inhibitors of Trypanosoma cruzi predicted by a computational drug repositioning method. Eur. J. Med. Chem., 2017, 132, 249-261.
[http://dx.doi.org/10.1016/j.ejmech.2017.03.063] [PMID: 28364659]
[118]
Haupt, V.J.; Aguilar Uvalle, J.E.; Salentin, S.; Daminelli, S.; Leonhardt, F.; Konc, J.; Schroeder, M. Computational drug repositioning by target hopping: a use case in chagas disease. Curr. Pharm. Des., 2016, 22(21), 3124-3134.
[http://dx.doi.org/10.2174/1381612822666160224143008] [PMID: 26873186]
[119]
Njogu, P.M.; Chibale, K. Recent developments in rationally designed multitarget antiprotozoan agents. Curr. Med. Chem., 2013, 20(13), 1715-1742.
[http://dx.doi.org/10.2174/0929867311320130010] [PMID: 23410169]

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