Login Register Cart 0
Generic placeholder image

Current Protein & Peptide Science

Editor-in-Chief

ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
General Review Article

Purines and Pyrimidines: Metabolism, Function and Potential as Therapeutic Options in Neurodegenerative Diseases

Author(s): Debanjan Kundu and Vikash Kumar Dubey*

Volume 22, Issue 2, 2021

Published on: 08 December, 2020

Page: [170 - 189] Pages: 20

DOI: 10.2174/1389203721999201208200605

Price: $65

Abstract

Various neurodegenerative disorders have various molecular origins but some common molecular mechanisms. In the current scenario, there are very few treatment regimens present for advanced neurodegenerative diseases. In this context, there is an urgent need for alternate options in the form of natural compounds with an ameliorating effect on patients. There have been individual scattered experiments trying to identify potential values of various intracellular metabolites. Purines and Pyrimidines, which are vital molecules governing various aspects of cellular biochemical reactions, have been long sought as crucial candidates for the same, but there are still many questions that go unanswered. Some critical functions of these molecules associated with neuromodulation activities have been identified. They are also known to play a role in foetal neurodevelopment, but there is a lacuna in understanding their mechanisms. In this review, we have tried to assemble and identify the importance of purines and pyrimidines, connecting them with the prevalence of neurodegenerative diseases. The leading cause of this class of diseases is protein misfolding and the formation of amyloids. A direct correlation between loss of balance in cellular homeostasis and amyloidosis is yet an unexplored area. This review aims at bringing the current literature available under one umbrella serving as a foundation for further extensive research in this field of drug development in neurodegenerative diseases.

Keywords: Purines, pyrimidines, neurodegenerative diseases, amyloidosis, purinergic signalling, nucleosides.

« Previous Next »
Graphical Abstract

[1]
Sebastián-Serrano, Á.; de Diego-García, L.; di Lauro, C.; Bianchi, C.; Díaz-Hernández, M. Nucleotides regulate the common molecular mechanisms that underlie neurodegenerative diseases; Therapeutic implications. Brain Res. Bull., 2019, 151, 84-91.
[http://dx.doi.org/10.1016/j.brainresbull.2019.01.031] [PMID: 30721769]
[2]
Sayed, R.H.; Hawkins, P.N.; Lachmann, H.J. Emerging treatments for amyloidosis. Kidney Int., 2015, 87(3), 516-526.
[http://dx.doi.org/10.1038/ki.2014.368] [PMID: 25469850]
[3]
Dubey, V.K.; Lee, J.; Blaber, M. Redesigning symmetry-related “mini-core” regions of FGF-1 to increase primary structure symmetry: thermodynamic and functional consequences of structural symmetry. Protein Sci., 2005, 14(9), 2315-2323.
[http://dx.doi.org/10.1110/ps.051494405] [PMID: 16081654]
[4]
Kundu, D.; Prerna, K.; Chaurasia, R.; Bharty, M.K.; Dubey, V.K. Advances in protein misfolding, amyloidosis and its correlation with human diseases 3 Biotech , 2020, 10(5), 193.
[5]
Ashraf, G.; Greig, N.H.; Khan, A.T.; Hassan, I.; Tabrez, S.; Shakil, S.; Sheikh, A.I.; Zaidi, K.S.; Wali, A.M.; Jabi, R.M.; Fitz, K. C.; Naeem, A.; Alhazza, M. I.; Damanhouri, A. G.; Kamal, A. M. Protein misfolding and aggregation in Alzheimer's Disease and Type 2 Diabetes Mellitus. CNS Neurol. Disord. Drug Target., 2014, 13(7), 1280 -1293 .
[6]
Cummings, J.; Lee, G.; Ritter, A.; Zhong, K. Alzheimer’s disease drug development pipeline: 2018. Alzheimers Dement. (N. Y.), 2018, 4, 195-214.
[http://dx.doi.org/10.1016/j.trci.2018.03.009] [PMID: 29955663]
[7]
Butterfield, D.A.; Swomley, A.M.; Sultana, R. Amyloid β-peptide (1-42)-induced oxidative stress in Alzheimer disease: importance in disease pathogenesis and progression. Antioxid. Redox Signal., 2013, 19(8), 823-835.
[http://dx.doi.org/10.1089/ars.2012.5027] [PMID: 23249141]
[8]
Kerr, J.S.; Adriaanse, B.A.; Greig, N.H.; Mattson, M.P.; Cader, M.Z.; Bohr, V.A.; Fang, E.F. Mitophagy and Alzheimer’s disease: cellular and molecular mechanisms. Trends Neurosci., 2017, 40(3), 151-166.
[http://dx.doi.org/10.1016/j.tins.2017.01.002] [PMID: 28190529]
[9]
Salavadores, N.; Sanhueza, M.; Manque, P.; Court, F. Axonal Degeneration during Aging and its Functional Role in Neurodegenerative Disorders. Front. Neurosci., 2017, 11 , 451 .
[10]
Franco, R.; Navarro, G. Adenosine A2A Receptor Antagonists in neurodegenerative Diseases: Huge potential and Huge Challenges Frontiers in Psychiatry 2018, 9 , 68 .
[11]
Rahman, A. The role of adenosine in Alzheimer’s disease. Curr. Neuropharmacol., 2009, 7(3), 207-216.
[http://dx.doi.org/10.2174/157015909789152119] [PMID: 20190962]
[12]
Hussain, R.; Zubair, H.; Pursell, S.; Shahab, M. Neurodegenerative Diseases: Regenerative Mechanisms and Novel Therapeutic Approaches. Brain Sci., 2018, 8(9), 177.
[http://dx.doi.org/10.3390/brainsci8090177] [PMID: 30223579]
[13]
Woolley, J.D.; Khan, B.K.; Murthy, N.K.; Miller, B.L.; Rankin, K.P. The diagnostic challenge of psychiatric symptoms in neurodegenerative disease: rates of and risk factors for prior psychiatric diagnosis in patients with early neurodegenerative disease. J. Clin. Psychiatry, 2011, 72(2), 126-133.
[http://dx.doi.org/10.4088/JCP.10m06382oli] [PMID: 21382304]
[14]
Thompson, L.M. Neurodegeneration: a question of balance. Nature, 2008, 452(7188), 707-708.
[http://dx.doi.org/10.1038/452707a] [PMID: 18401401]
[15]
Schneider, J.S.; Sendek, S.; Yang, C. Relationship between motor symptoms, cognition, and demographic characteristics in treated mild/moderate Parkinson’s disease. PLoS One, 2015, 10(4), e0123231.
[http://dx.doi.org/10.1371/journal.pone.0123231] [PMID: 25905783]
[16]
Zhao, T.; Hong, Y.; Li, X.J.; Li, S.H. Subcellular clearance and accumulation of Huntington disease protein. A mini-review. Front. Mol. Neurosci., 2016, 9, 27.
[http://dx.doi.org/10.3389/fnmol.2016.00027] [PMID: 27147961]
[17]
Roxburgh, R.H.; Smith, C.O.; Lim, J.G.; Bachman, D.F.; Byrd, E.; Bird, T.D. The unique co-occurrence of spinocerebellar ataxia type 10 (SCA10) and Huntington disease. J. Neurol. Sci., 2013, 324(1-2), 176-178.
[http://dx.doi.org/10.1016/j.jns.2012.09.030] [PMID: 23083689]
[18]
Ryan, J.; Fransquet, P.; Wrigglesworth, J.; Lacaze, P. Phenotypic heterogeneity in dementia: A challenge for epidemiology and biomarker studies. Front. Public Health, 2018, 6, 181.
[http://dx.doi.org/10.3389/fpubh.2018.00181] [PMID: 29971228]
[19]
McKeith, I.G.; Dickson, D.W.; Lowe, J.; Emre, M.; O’Brien, J.T.; Feldman, H.; Cummings, J.; Duda, J.E.; Lippa, C.; Perry, E.K.; Aarsland, D.; Arai, H.; Ballard, C.G.; Boeve, B.; Burn, D.J.; Costa, D.; Del Ser, T.; Dubois, B.; Galasko, D.; Gauthier, S.; Goetz, C.G.; Gomez-Tortosa, E.; Halliday, G.; Hansen, L.A.; Hardy, J.; Iwatsubo, T.; Kalaria, R.N.; Kaufer, D.; Kenny, R.A.; Korczyn, A.; Kosaka, K.; Lee, V.M.; Lees, A.; Litvan, I.; Londos, E.; Lopez, O.L.; Minoshima, S.; Mizuno, Y.; Molina, J.A.; Mukaetova-Ladinska, E.B.; Pasquier, F.; Perry, R.H.; Schulz, J.B.; Trojanowski, J.Q.; Yamada, M. Consortium on DLB. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology, 2005, 65(12), 1863-1872.
[http://dx.doi.org/10.1212/01.wnl.0000187889.17253.b1] [PMID: 16237129]
[20]
Delgado-Morales, R.; Esteller, M. Opening up the DNA methylome of dementia. Mol. Psychiatry, 2017, 22(4), 485-496.
[http://dx.doi.org/10.1038/mp.2016.242] [PMID: 28044062]
[21]
Duyckaerts, C.; Dickson, D. Neurodegeneration: The Molecular Pathology of Dementia and Movement Disorders Wiley-Blackwell: West Sussex,, 2011, pp. pp 62-91.
[http://dx.doi.org/10.1002/9781444341256.ch10]
[22]
Ansolega, B.; Jove, M.; Schluter, A. Deregulation of purine metabolism in Alzheimer's Disease Neurobiology of Aging, 2014.
[23]
Fumagalli, M.; Lecca, D.; Abbracchio, M.P.; Ceruti, S. Pathophysiological Role of Purines and Pyrimidines in Neurodevelopment: Unveiling New Pharmacological Approaches to Congenital Brain Diseases. Front. Pharmacol., 2017, 8, 941.
[http://dx.doi.org/10.3389/fphar.2017.00941] [PMID: 29375373]
[24]
Gallinaro, L.; Crovatto, K.; Rampazzo, C.; Pontarin, G.; Ferraro, P.; Milanesi, E.; Reichard, P.; Bianchi, V. Human mitochondrial 5′-deoxyribonucleotidase. Overproduction in cultured cells and functional aspects. J. Biol. Chem., 2002, 277(38), 35080-35087.
[http://dx.doi.org/10.1074/jbc.M203755200] [PMID: 12124385]
[25]
Kovács, Z.; Dobolyi, A.; Kékesi, K.A.; Juhász, G. 5′-nucleotidases, nucleosides and their distribution in the brain: pathological and therapeutic implications. Curr. Med. Chem., 2013, 20(34), 4217-4240.
[http://dx.doi.org/10.2174/0929867311320340003] [PMID: 23992313]
[26]
Volonté, C.; D’Ambrosi, N. Membrane compartments and purinergic signalling: the purinome, a complex interplay among ligands, degrading enzymes, receptors and transporters. FEBS J., 2009, 276(2), 318-329.
[http://dx.doi.org/10.1111/j.1742-4658.2008.06793.x] [PMID: 19076212]
[27]
Kovács, Z.; Dobolyi, A.; Juhász, G.; Kékesi, K.A. Nucleoside map of the human central nervous system. Neurochem. Res., 2010, 35(3), 452-464.
[http://dx.doi.org/10.1007/s11064-009-0080-z] [PMID: 19856099]
[28]
Burnstock, G. Pathophysiology and therapeutic potential of purinergic signaling. Pharmacol. Rev., 2006, 58(1), 58-86.
[http://dx.doi.org/10.1124/pr.58.1.5] [PMID: 16507883]
[29]
Burnstock, G.; Knight, G.E. Cellular distribution and functions of P2 receptor subtypes in different systems. Int. Rev. Cytol., 2004, 240, 31-304.
[http://dx.doi.org/10.1016/S0074-7696(04)40002-3] [PMID: 15548415]
[30]
Burnstock, G. Purinergic receptors. J. Theor. Biol., 1976, 62(2), 491-503.
[http://dx.doi.org/10.1016/0022-5193(76)90133-8] [PMID: 994531]
[31]
Burnstock, G. Purine and purinergic receptors. Brain Neurosci. Adv., 2018, 2
[http://dx.doi.org/10.1177/2398212818817494] [PMID: 32166165]
[32]
Owen, M.C.; Gnutt, D.; Gao, M.; Wärmländer, S.K.T.S.; Jarvet, J.; Gräslund, A.; Winter, R.; Ebbinghaus, S.; Strodel, B. Effects of in vivo conditions on amyloid aggregation. Chem. Soc. Rev., 2019, 48(14), 3946-3996.
[http://dx.doi.org/10.1039/C8CS00034D] [PMID: 31192324]
[33]
Fields, R.D.; Stevens, B. ATP: an extracellular signaling molecule between neurons and glia. Trends Neurosci., 2000, 23(12), 625-633.
[http://dx.doi.org/10.1016/S0166-2236(00)01674-X] [PMID: 11137153]
[34]
Newman, E.A. Glial cell inhibition of neurons by release of ATP. J. Neurosci., 2003, 23(5), 1659-1666.
[http://dx.doi.org/10.1523/JNEUROSCI.23-05-01659.2003] [PMID: 12629170]
[35]
Burnstock, G. Introduction: ATP and its metabolites as potent extracellular agonists.Purinergic Receptors and Signalling. Schwiebert, E.M., Ed. Current Topicsin MembranesAcademic Press: San Diego, CA,; , 2003, 54, pp. pp 1-27.
[http://dx.doi.org/10.1016/S1063-5823(03)01001-9]
[36]
Abbracchio, M.P.; Burnstock, G.; Boeynaems, J.M.; Barnard, E.A.; Boyer, J.L.; Kennedy, C.; Knight, G.E.; Fumagalli, M.; Gachet, C.; Jacobson, K.A.; Weisman, G.A. International Union of Pharmacology LVIII: update on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy. Pharmacol. Rev., 2006, 58(3), 281-341.
[http://dx.doi.org/10.1124/pr.58.3.3] [PMID: 16968944]
[37]
Bonan, C.D. Ectonucleotidases and nucleotide/nucleoside transporters as pharmacological targets for neurological disorders. CNS Neurol. Disord. Drug Targets, 2012, 11(6), 739-750.
[http://dx.doi.org/10.2174/187152712803581092] [PMID: 22963442]
[38]
Grazia, T.M. Inborn errors in purine metabolism: role of 5′-nucleotidases and their involvement in the etiology of neurological impairments. Nucleosides Nucleotides Nucleic Acids, 2011, 30(12), 1276-1283.
[http://dx.doi.org/10.1080/15257770.2011.616869] [PMID: 22132987]
[39]
Cunha, R.A. Adenosine as a neuromodulator and as a homeostatic regulator in the nervous system: different roles, different sources and different receptors. Neurochem. Int., 2001, 38(2), 107-125.
[http://dx.doi.org/10.1016/S0197-0186(00)00034-6] [PMID: 11137880]
[40]
Cunha-Reis, D.; Fontinha, B.M.; Ribeiro, J.A.; Sebastião, A.M. Tonic adenosine A1 and A2A receptor activation is required for the excitatory action of VIP on synaptic transmission in the CA1 area of the hippocampus. Neuropharmacology, 2007, 52(2), 313-320.
[http://dx.doi.org/10.1016/j.neuropharm.2006.08.003] [PMID: 17030044]
[41]
De Mendonca, A.; Ribeiro, J.A. Adenosine and synaptic plasticity. Drug Dev. Res., 2001, 52, 283-290.
[http://dx.doi.org/10.1002/ddr.1125]
[42]
Pereira, G.S.; Mello e Souza, T.; Vinadé, E.R.; Choi, H.; Rodrigues, C.; Battastini, A.M.; Izquierdo, I.; Sarkis, J.J.; Bonan, C.D. Blockade of adenosine A1 receptors in the posterior cingulate cortex facilitates memory in rats. Eur. J. Pharmacol., 2002, 437(3), 151-154.
[http://dx.doi.org/10.1016/S0014-2999(02)01307-9] [PMID: 11890903]
[43]
Ikeda, M.; Mackay, K.B.; Dewar, D.; McCulloch, J. Differential alterations in adenosine A1 and kappa 1 opioid receptors in the striatum in Alzheimer’s disease. Brain Res., 1993, 616(1-2), 211-217.
[http://dx.doi.org/10.1016/0006-8993(93)90211-5] [PMID: 8395303]
[44]
Kalaria, R.N.; Sromek, S.; Wilcox, B.J.; Unnerstall, J.R. Hippocampal adenosine A1 receptors are decreased in Alzheimer’s disease. Neurosci. Lett., 1990, 118(2), 257-260.
[http://dx.doi.org/10.1016/0304-3940(90)90641-L] [PMID: 2274280]
[45]
Albasanz, J.L.; Perez, S.; Barrachina, M.; Ferrer, I.; Martín, M. Up-regulation of adenosine receptors in the frontal cortex in Alzheimer's disease brain. Pathol., 2008, 18, 211-219.
[46]
Arendash, G.W.; Schleif, W.; Rezai-Zadeh, K.; Jackson, E.K.; Zacharia, L.C.; Cracchiolo, J.R.; Shippy, D.; Tan, J. Caffeine protects Alzheimer’s mice against cognitive impairment and reduces brain β-amyloid production. Neuroscience, 2006, 142(4), 941-952.
[http://dx.doi.org/10.1016/j.neuroscience.2006.07.021] [PMID: 16938404]
[47]
Pinna, A.; Corsi, C.; Carta, A.R.; Valentini, V.; Pedata, F.; Morelli, M. Modification of adenosine extracellular levels and adenosine A(2A) receptor mRNA by dopamine denervation. Eur. J. Pharmacol., 2002, 446(1-3), 75-82.
[http://dx.doi.org/10.1016/S0014-2999(02)01818-6] [PMID: 12098587]
[48]
Rebola, N.; Porciúncula, L.O.; Lopes, L.V.; Oliveira, C.R.; Soares-da-Silva, P.; Cunha, R.A. Long-term effect of convulsive behavior on the density of adenosine A1 and A 2A receptors in the rat cerebral cortex. Epilepsia, 2005, 46(Suppl. 5), 159-165.
[http://dx.doi.org/10.1111/j.1528-1167.2005.01026.x] [PMID: 15987272]
[49]
Wang, L. Mitochondrial purine and pyrimidine metabolism and beyond. Nucleosides Nucleotides Nucleic Acids, 2016, 35(10-12), 578-594, 578-594.
[http://dx.doi.org/10.1080/15257770.2015.1125001] [PMID: 27906631]
[50]
Geiger, J.D.; Buscemi, L.; Fotheringham, J.A. Role of adenosine in the control of inflammatory events associated with acute and chronic neurodegenerative disorders.Adenosine receptors: Therapeutic aspects for inflammatory and immune diseases. Cronstein, B.; Szabo, C.; Hasko, G., Eds.; Taylor and Francis; , 2006.
[51]
Cunha, G.M.A.; Canas, P.M.; Chen, J.F.; Oliviera, C.R.; Cunha, R.A. Blocked of adenosine A2A receptors prevents amyloid (Aβ1−42)-induced synaptotoxicity and memory impairment in rodents. Purinergic Signal., 2006, 2, 135-136.
[52]
Byeon, J.J.; Park, M.H.; Shin, S.H.; Park, Y.; Lee, B.I.; Choi, J.M.; Kim, N.; Park, S.J.; Park, M.J.; Lim, J.H.; Na, Y.G.; Shin, Y.G. in vitro, In Silico, and In Vivo Assessments of Pharmacokinetic Properties of ZM241385. Molecules, 2020, 25(5), 1106.
[http://dx.doi.org/10.3390/molecules25051106] [PMID: 32131453]
[53]
Fasullo, M.; Endres, L. Nucleotide salvage deficiencies, DNA damage and neurodegeneration. Int. J. Mol. Sci., 2015, 16(5), 9431-9449.
[http://dx.doi.org/10.3390/ijms16059431] [PMID: 25923076]
[54]
Frampton, M.; Harvey, R.J.; Kirchner, V. Propentofylline for dementia. Cochrane Database Syst. Rev., 2003, (2), CD002853.
[PMID: 12804440]
[55]
Zhang, J.M.; Wang, H.K.; Ye, C.Q.; Ge, W; Chen, Y.; Jiang, Z.L.; Wu, C.P; Poo, MM; Duan, S. ATP released by astrocytes mediates glutamatergic activity-dependent heterosynaptic suppression Neuron, 2003, 40, 982-983.
[http://dx.doi.org/10.1016/S0896-6273(03)00717-7]
[56]
Gourine, A.V.; Dale, N.; Gourine, V.N.; Spyer, K.M. Fever in systemic inflammation: roles of purines. Front. Biosci., 2004, 9, 1011-1022.
[http://dx.doi.org/10.2741/1301] [PMID: 14766427]
[57]
Lara, D.R.; Souza, D.O. Schizophrenia: a purinergic hypothesis. Med. Hypotheses, 2000, 54(2), 157-166.
[http://dx.doi.org/10.1054/mehy.1999.0003] [PMID: 10790742]
[58]
Machado-Vieira, R.; Lara, D.R.; Souza, D.O.; Kapczinski, F. Purinergic dysfunction in mania: an integrative model. Med. Hypotheses, 2002, 58(4), 297-304.
[http://dx.doi.org/10.1054/mehy.2001.1543] [PMID: 12027524]
[59]
Même, W.; Ezan, P.; Venance, L.; Glowinski, J.; Giaume, C. ATP-induced inhibition of gap junctional communication is enhanced by interleukin-1 beta treatment in cultured astrocytes. Neuroscience, 2004, 126(1), 95-104.
[http://dx.doi.org/10.1016/j.neuroscience.2004.03.031] [PMID: 15145076]
[60]
Han, W.J.; Kim, S.Y.; Lee, Y.B. Neuroprotective effect of extracellular ATP induced interleukin-10 expression in an in vitro model of brain ischemia2004 Abstract Viewer/Itinerary Planner; Program no. 100.1. Society for Neuroscience: Washington, DC,; , 2004.
[61]
Neary, J.T.; Kang, Y.; Tran, M.; Feld, J. Traumatic injury activates protein kinase B/Akt in cultured astrocytes: role of extracellular ATP and P2 purinergic receptors. J. Neurotrauma, 2005, 22(4), 491-500.
[http://dx.doi.org/10.1089/neu.2005.22.491] [PMID: 15853465]
[62]
Di Liberto, V.; Mudò, G.; Garozzo, R.; Frinchi, M.; Fernandez- Dueñas, V.; Di Iorio, P.; Ciccarelli, R.; Caciagli, F.; Condorelli, D.F.; Ciruela, F.; Belluardo, N. The Guanine-Based Purinergic System: The Tale of An Orphan Neuromodulation. Front. Pharmacol., 2016, 7, 158.
[http://dx.doi.org/10.3389/fphar.2016.00158] [PMID: 27378923]
[63]
Giuliani, P.; Ballerini, P.; Ciccarelli, R.; Buccella, S.; Romano, S.; D’Alimonte, I.; Poli, A.; Beraudi, A.; Peña, E.; Jiang, S.; Rathbone, M.P.; Caciagli, F.; Di Iorio, P. Tissue distribution and metabolism of guanosine in rats following intraperitoneal injection. J. Biol. Regul. Homeost. Agents, 2012, 26(1), 51-65.
[PMID: 22475097]
[64]
Uemura, Y.; Miller, J.M.; Matson, W.R.; Beal, M.F. Neurochemical analysis of focal ischemia in rats. Stroke, 1991, 22(12), 1548-1553.
[http://dx.doi.org/10.1161/01.STR.22.12.1548] [PMID: 1720576]
[65]
Stentoft, C.; Vestergaard, M.; Løvendahl, P.; Kristensen, N.B.; Moorby, J.M.; Jensen, S.K. Simultaneous quantification of purine and pyrimidine bases, nucleosides and their degradation products in bovine blood plasma by high performance liquid chromatography tandem mass spectrometry. J. Chromatogr. A, 2014, 1356, 197-210.
[http://dx.doi.org/10.1016/j.chroma.2014.06.065] [PMID: 25017393]
[66]
Dal-Cim, T.; Ludka, F.K.; Martins, W.C.; Reginato, C.; Parada, E.; Egea, J.; López, M.G.; Tasca, C.I. Guanosine controls inflammatory pathways to afford neuroprotection of hippocampal slices under oxygen and glucose deprivation conditions. J. Neurochem., 2013, 126(4), 437-450.
[http://dx.doi.org/10.1111/jnc.12324] [PMID: 23713463]
[67]
Bau, C.; Middlemiss, P.J.; Hindley, S.; Jiang, S.; Ciccarelli, R.; Caciagli, F.; Diiorio, P.; Werstiuk, E.S.; Rathbone, M.P. Guanosine stimulates neurite outgrowth in PC12 cells via activation of heme oxygenase and cyclic GMP. Purinergic Signal., 2005, 1(2), 161-172.
[http://dx.doi.org/10.1007/s11302-005-6214-0] [PMID: 18404501]
[68]
Su, C.; Wang, P.; Jiang, C.; Ballerini, P.; Caciagli, F.; Rathbone, M.P.; Jiang, S. Guanosine promotes proliferation of neural stem cells through cAMP-CREB pathway. J. Biol. Regul. Homeost. Agents, 2013, 27(3), 673-680.
[PMID: 24152836]
[69]
Molz, S.; Dal-Cim, T.; Budni, J.; Martín-de-Saavedra, M.D.; Egea, J.; Romero, A.; del Barrio, L.; Rodrigues, A.L.; López, M.G.; Tasca, C.I. Neuroprotective effect of guanosine against glutamate-induced cell death in rat hippocampal slices is mediated by the phosphatidylinositol-3 kinase/Akt/ glycogen synthase kinase 3β pathway activation and inducible nitric oxide synthase inhibition. J. Neurosci. Res., 2011, 89(9), 1400-1408.
[http://dx.doi.org/10.1002/jnr.22681] [PMID: 21671255]
[70]
Dal-Cim, T.; Molz, S.; Egea, J.; Parada, E.; Romero, A.; Budni, J.; Martín de Saavedra, M.D.; del Barrio, L.; Tasca, C.I.; López, M.G. Guanosine protects human neuroblastoma SH-SY5Y cells against mitochondrial oxidative stress by inducing heme oxigenase-1 via PI3K/Akt/GSK-3β pathway. Neurochem. Int., 2012, 61(3), 397-404.
[http://dx.doi.org/10.1016/j.neuint.2012.05.021] [PMID: 22683349]
[71]
Bettio, L.E.; Cunha, M.P.; Budni, J.; Pazini, F.L.; Oliveira, Á.; Colla, A.R.; Rodrigues, A.L. Guanosine produces an antidepressant-like effect through the modulation of NMDA receptors, nitric oxide-cGMP and PI3K/mTOR pathways. Behav. Brain Res., 2012, 234(2), 137-148.
[http://dx.doi.org/10.1016/j.bbr.2012.06.021] [PMID: 22743004]
[72]
Brassai, A.; Suvanjeiev, R.G.; Bán, E.G.; Lakatos, M. Role of synaptic and nonsynaptic glutamate receptors in ischaemia induced neurotoxicity. Brain Res. Bull., 2015, 112, 1-6.
[http://dx.doi.org/10.1016/j.brainresbull.2014.12.007] [PMID: 25540918]
[73]
Ferreira, A.G.; da Cunha, A.A.; Scherer, E.B.; Machado, F.R.; da Cunha, M.J.; Braga, A.; Mussulini, B.H.; Moreira, J.D.; Wofchuk, S.; Souza, D.O.; Wyse, A.T. Evidence that hyperprolinemia alters glutamatergic homeostasis in rat brain: neuroprotector effect of guanosine. Neurochem. Res., 2012, 37(1), 205-213.
[http://dx.doi.org/10.1007/s11064-011-0604-1] [PMID: 21935728]
[74]
Kovacs, Z.; Kekesi, K.A.; Juhasz, G.; Barna, J.; Heja, L.; Lakatos, R. Non-adenosine nucleoside inosine, guanosine and uridine as promising anti-epileptic drugs: a summary of current literature Mini. Rev. Med.Chem., 2015, 14, 1033-1042.
[75]
Torres, F.V.; da Silva Filho, M.; Antunes, C.; Kalinine, E.; Antoniolli, E.; Portela, L.V.; Souza, D.O.; Tort, A.B. Electrophysiological effects of guanosine and MK-801 in a quinolinic acid-induced seizure model. Exp. Neurol., 2010, 221(2), 296-306.
[http://dx.doi.org/10.1016/j.expneurol.2009.11.013] [PMID: 19948169]
[76]
Bellaver, B.; Souza, D.G.; Bobermin, L.D.; Gonçalves, C.A.; Souza, D.O.; Quincozes-Santos, A. Guanosine inhibits LPS-induced pro-inflammatory response and oxidative stress in hippocampal astrocytes through the heme oxygenase-1 pathway. Purinergic Signal., 2015, 11(4), 571-580.
[http://dx.doi.org/10.1007/s11302-015-9475-2] [PMID: 26431832]
[77]
Hansel, G.; Tonon, A.C.; Guella, F.L.; Pettenuzzo, L.F.; Duarte, T.; Duarte, M.M.M.F.; Oses, J.P.; Achaval, M.; Souza, D.O. Guanosine Protects Against Cortical Focal Ischemia. Involvement of Inflammatory Response. Mol. Neurobiol., 2015, 52(3), 1791-1803.
[http://dx.doi.org/10.1007/s12035-014-8978-0] [PMID: 25394382]
[78]
Roos, D.H.; Puntel, R.L.; Santos, M.M.; Souza, D.O.; Farina, M.; Nogueira, C.W.; Aschner, M.; Burger, M.E.; Barbosa, N.B.; Rocha, J.B. Guanosine and synthetic organoselenium compounds modulate methylmercury-induced oxidative stress in rat brain cortical slices: involvement of oxidative stress and glutamatergic system. Toxicol. in vitro, 2009, 23(2), 302-307.
[http://dx.doi.org/10.1016/j.tiv.2008.12.020] [PMID: 19162164]
[79]
Paniz, L.G.; Calcagnotto, M.E.; Pandolfo, P.; Machado, D.G.; Santos, G.F.; Hansel, G.; Almeida, R.F.; Bruch, R.S.; Brum, L.M.; Torres, F.V.; de Assis, A.M.; Rico, E.P.; Souza, D.O. Neuroprotective effects of guanosine administration on behavioral, brain activity, neurochemical and redox parameters in a rat model of chronic hepatic encephalopathy. Metab. Brain Dis., 2014, 29(3), 645-654.
[http://dx.doi.org/10.1007/s11011-014-9548-x] [PMID: 24788896]
[80]
Petronilho, F.; Périco, S.R.; Vuolo, F.; Mina, F.; Constantino, L.; Comim, C.M.; Quevedo, J.; Souza, D.O.; Dal-Pizzol, F. Protective effects of guanosine against sepsis-induced damage in rat brain and cognitive impairment. Brain Behav. Immun., 2012, 26(6), 904-910.
[http://dx.doi.org/10.1016/j.bbi.2012.03.007] [PMID: 22497789]
[81]
Cavdar, H.; Senturk, M.; Guney, M.; Durdagi, S.; Kayik, G.; Supuran, C.T.; Ekinci, D. Inhibition of acetylcholinesterase and butyrylcholinesterase with uracil derivatives: kinetic and computational studies. J. Enzyme Inhib. Med. Chem., 2019, 34(1), 429-437.
[http://dx.doi.org/10.1080/14756366.2018.1543288] [PMID: 30734597]
[82]
Kundu, D.; Umesh, ; Dubey, V.K. Interaction of selected biomolecules and metabolites with amyloidogenic proteins. J. Biomol. Struct. Dyn., 2020, 1-10.
[http://dx.doi.org/10.1080/07391102.2020.1760138] [PMID: 32329418]
[83]
Connolly, G.P.; Duley, J.A. Uridine and its nucleotides: biological actions, therapeutic potentials. Trends Pharmacol. Sci., 1999, 20(5), 218-225.
[http://dx.doi.org/10.1016/S0165-6147(99)01298-5] [PMID: 10354618]
[84]
Löffler, M.; Carrey, E.A.; Zameitat, E. New perspectives on the roles of pyrimidines in the central nervous system. Nucleosides Nucleotides Nucleic Acids, 2018, 37(5), 290-306.
[http://dx.doi.org/10.1080/15257770.2018.1453076] [PMID: 29693489]
[85]
Kimura, T.; Ho, I. K.; Yamamoto, I Uridine receptor: discovery and its involvement in sleep mechanism Sleep, 2001, 24, 251-60.
[86]
Ipata, P.L.; Camici, M.; Micheli, V.; Tozz, M.G. Metabolic network of nucleosides in the brain. Curr. Top. Med. Chem., 2011, 11(8), 909-922.
[http://dx.doi.org/10.2174/156802611795347555] [PMID: 21401502]
[87]
Cappiello, M.; Mascia, L.; Scolozzi, C.; Giorgelli, F.; Ipata, P.L. in vitro assessment of salvage pathways for pyrimidine bases in rat liver and brain. Biochim. Biophys. Acta, 1998, 1425(2), 273-281.
[http://dx.doi.org/10.1016/S0304-4165(98)00071-3] [PMID: 9795240]
[88]
Choi, J.W.; Shin, C.Y.; Choi, M.S.; Yoon, S.Y.; Ryu, J.H.; Lee, J.C.; Kim, W.K.; El Kouni, M.H.; Ko, K.H. Uridine protects cortical neurons from glucose deprivation-induced death: possible role of uridine phosphorylase. J. Neurotrauma, 2008, 25(6), 695-707.
[http://dx.doi.org/10.1089/neu.2007.0409] [PMID: 18457515]
[89]
Pohle, W.; Matthies, H. Incorporation of RNA-precursors into neuronal and glial cells of rat brain during a learning experiment. Brain Res., 1974, 65(2), 231-237.
[http://dx.doi.org/10.1016/0006-8993(74)90035-3] [PMID: 4423991]
[90]
Saydoff, J.A.; Olariu, A.; Sheng, J.; Hu, Z.; Li, Q.; Garcia, R.; Pei, J.; Sun, G.Y.; von Borstel, R. Uridine prodrug improves memory in Tg2576 and TAPP mice and reduces pathological factors associated with Alzheimer’s disease in related models. J. Alzheimers Dis., 2013, 36(4), 637-657.
[http://dx.doi.org/10.3233/JAD-130059] [PMID: 23648515]
[91]
Kovács, Z.; Kékesi, K.A.; Juhász, G.; Dobolyi, Á. The antiepileptic potential of nucleosides. Curr. Med. Chem., 2014, 21(6), 788-821.
[http://dx.doi.org/10.2174/1381612819666131119154505] [PMID: 24251559]
[92]
Grieb, P. Neuroprotective properties of citicoline: facts, doubts and unresolved issues. CNS Drugs, 2014, 28(3), 185-193.
[http://dx.doi.org/10.1007/s40263-014-0144-8] [PMID: 24504829]
[93]
Williams, M. Purinergic neurotransmission.Neuropsychopharmacology - The Fifth Generation of Progress pp-191-206 Philadelphia. Davies, K.L.; Charney, D.; Coyle, J.T.; Nemeroff, C., Eds.; Lippincott, Williams and Wilkins; , 2002.
[94]
Williams, M.; Burnstock, G. Purinergic neurotransmission and neuromodulation: a historical perspective.Purinergic approaches in experimental therapeutics. Jacobson, K.A.; Jarvis, M.F., Eds.; Wiley Liss: New York; , 1997, pp. pp 3-26.
[95]
Ralevic, V.; Burnstock, G. Receptors for purines and pyrimidines. Pharmacol. Rev., 1998, 50(3), 413-492.
[PMID: 9755289]
[96]
Neary, J.T.; Rathbone, M.P.; Cattabeni, F.; Abbracchio, M.P.; Burnstock, G. Trophic actions of extracellular nucleotides and nucleosides on glial and neuronal cells. Trends Neurosci., 1996, 19(1), 13-18.
[http://dx.doi.org/10.1016/0166-2236(96)81861-3] [PMID: 8787135]
[97]
Tasca, C.I.; Lanznaster, D.; Oliveira, K.A.; Fernández-Dueñas, V.; Ciruela, F. Neuromodulatory Effects of Guanine-Based Purines in Health and Disease. Front. Cell. Neurosci., 2018, 12, 376.
[http://dx.doi.org/10.3389/fncel.2018.00376] [PMID: 30459558]
[98]
Lanznaster, D.; Mack, J.M.; Coelho, V.; Ganzella, M.; Almeida, R.F.; Dal-Cim, T.; Hansel, G.; Zimmer, E.R.; Souza, D.O.; Prediger, R.D.; Tasca, C.I. Guanosine Prevents Anhedonic-Like Behavior and Impairment in Hippocampal Glutamate Transport Following Amyloid-β1-40 Administration in Mice. Mol. Neurobiol., 2017, 54(7), 5482-5496.
[http://dx.doi.org/10.1007/s12035-016-0082-1] [PMID: 27599498]
[99]
Masters, C.L.; Selkoe, D.J. Biochemistry of amyloid β-protein and amyloid deposits in Alzheimer disease. Cold Spring Harb. Perspect. Med., 2012, 2(6), a006262.
[http://dx.doi.org/10.1101/cshperspect.a006262] [PMID: 22675658]
[100]
Su, C.; Elfeki, N.; Ballerini, P.; D’Alimonte, I.; Bau, C.; Ciccarelli, R.; Caciagli, F.; Gabriele, J.; Jiang, S. Guanosine improves motor behavior, reduces apoptosis, and stimulates neurogenesis in rats with parkinsonism. J. Neurosci. Res., 2009, 87(3), 617-625.
[http://dx.doi.org/10.1002/jnr.21883] [PMID: 18816792]
[101]
Olanow, C.W.; Tatton, W.G. Etiology and pathogenesis of Parkinson’s disease. Annu. Rev. Neurosci., 1999, 22, 123-144.
[http://dx.doi.org/10.1146/annurev.neuro.22.1.123] [PMID: 10202534]
[102]
Chen, X.; Xie, C.; Sun, L.; Ding, J.; Cai, H. Longitudinal Metabolomics Profiling of Parkinson’s Disease-Related α-Synuclein A53T Transgenic Mice. PLoS One, 2015, 10(8)
[http://dx.doi.org/10.1371/journal.pone.0136612] [PMID: 26317866]
[103]
Firestein, G.S. Anti-inflammatory effects of adenosine kinase inhibitorsin acute and chronic inflammation. Drug Dev. Res., 1996, 39, 371-376.
[http://dx.doi.org/10.1002/(SICI)1098-2299(199611/12)39:3/4<371::AID-DDR18>3.0.CO;2-4]
[104]
Hansel, G.; Ramos, D. B.; Delgado, C. A.; Souza, D. G.; Almeida, R. F.; Portela, L. V. The potential therapeutic effect of guanosine after cortical focal ischemia in rats PLoS One, 2014, 9, e90693.
[105]
Lanznaster, D.; Dal-Cim, T.; Piermartiri, T.C.; Tasca, C.I. Guanosine: a Neuromodulator with Therapeutic Potential in Brain Disorders. Aging Dis., 2016, 7(5), 657-679.
[http://dx.doi.org/10.14336/AD.2016.0208] [PMID: 27699087]
[106]
Soares, F. A.; Schmidt, A. P.; Farina, M.; Frizzo, M. E. S.; Tavares, R. G.; Portela, L. V. C. Anticonvulsant effect of GMP depends on its conversion to guanosine Brain Res., 2004, 1005, 182-186.
[http://dx.doi.org/10.1016/j.brainres.2004.01.053]
[107]
de Oliveira, D.L.; Horn, J.F.; Rodrigues, J.M.; Frizzo, M.E.S.; Moriguchi, E.; Souza, D.O.; Wofchuk, S. Quinolinic acid promotes seizures and decreases glutamate uptake in young rats: reversal by orally administered guanosine. Brain Res., 2004, 1018(1), 48-54.
[http://dx.doi.org/10.1016/j.brainres.2004.05.033] [PMID: 15262204]
[108]
Vincenzetti, S.; Pozlonetti, V.; Micozzi, D. Enzymology of Pyrimidine metabolism and Neurodegeneration. Curr. Med. Chem., 2016, 23(14), 1408-1031.
[109]
Cansev, M.; Ulus, I.H.; Wang, L.; Maher, T.J.; Wurtman, R.J. Restorative effects of uridine plus docosahexaenoic acid in a rat model of Parkinson’s disease. Neurosci. Res., 2008, 62(3), 206-209.
[http://dx.doi.org/10.1016/j.neures.2008.07.005] [PMID: 18761383]
[110]
Holguin, S.; Martinez, J.; Chow, C.; Wurtman, R. Dietary uridine enhances the improvement in learning and memory produced by administering DHA to gerbils. FASEB J., 2008, 22(11), 3938-3946.
[http://dx.doi.org/10.1096/fj.08-112425] [PMID: 18606862]
[111]
van Kuilenburg, A.B.; Dobritzsch, D.; Meijer, J.; Meinsma, R.; Benoist, J.F.; Assmann, B.; Schubert, S.; Hoffmann, G.F.; Duran, M.; de Vries, M.C.; Kurlemann, G.; Eyskens, F.J.; Greed, L.; Sass, J.O.; Schwab, K.O.; Sewell, A.C.; Walter, J.; Hahn, A.; Zoetekouw, L.; Ribes, A.; Lind, S.; Hennekam, R.C. Dihydropyrimidinase deficiency: Phenotype, genotype and structural consequences in 17 patients. Biochim. Biophys. Acta, 2010, 1802(7-8), 639-648.
[http://dx.doi.org/10.1016/j.bbadis.2010.03.013] [PMID: 20362666]

Rights & Permissions Print Cite
Article Metrics
25
© 2024 Bentham Science Publishers | Privacy Policy