Author(s):
Antony Justin, Meghana Basavaraj, Deepthi Murugan, Gaddam Narasimha Rao, Jeyaram Bharathi J
Email(s):
justin@jssuni.edu.in
DOI:
10.52711/0974-360X.2022.00505
Address:
Antony Justin*, Meghana Basavaraj, Deepthi Murugan, Gaddam Narasimha Rao, Jeyaram Bharathi J
Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty 643001, Nilgiris, Tamil Nadu, India.
*Corresponding Author
Published In:
Volume - 15,
Issue - 7,
Year - 2022
ABSTRACT:
Multiple sclerosis (MS) is one of the most affecting autoimmune neurodegenerative disease characterized by chronic neuroinflammation, demyelination and impaired neuronal conduction. The oligodendrocytes toxicity by inflammatory cytokines and oxy-radicals are considered to be the most important factor in demyelination of motor neurons. The dysfunction of neuronal A1 adenosine receptor (A1AR) contributes to the demyelination of neurons by triggering the pro-inflammatory cytokines, oxy-radicals and neuroinflammatory cascades. In MS pathogenesis, Antigen presenting cells, MHC protein, CD4+T-cells, GM-CSF along with effector cells enhance the activation of macrophages in adenosinergic declined conditions, where it shows cumulative effects which leads to oligodendrocytes toxicity and demyelination of motor neurons. In general, A1AR is mainly expressed in macrophage lineage cells in central nervous system which could control the macrophage activation upon stimulation by its agonists. In this review, we have mainly emphasized on the pathogenesis of MS and highlighted the importance of adenosinergic system in reversing the molecular events in MS. In addition, we have discussed about the beneficial role of A1AR agonists in MS management.
Cite this article:
Antony Justin, Meghana Basavaraj, Deepthi Murugan, Gaddam Narasimha Rao, Jeyaram Bharathi J. Role of A1 Adenosinergic System in Multiple Sclerosis and Possible Therapeutic Strategy. Research Journal of Pharmacy and Technology. 2022; 15(7):3025-8. doi: 10.52711/0974-360X.2022.00505
Cite(Electronic):
Antony Justin, Meghana Basavaraj, Deepthi Murugan, Gaddam Narasimha Rao, Jeyaram Bharathi J. Role of A1 Adenosinergic System in Multiple Sclerosis and Possible Therapeutic Strategy. Research Journal of Pharmacy and Technology. 2022; 15(7):3025-8. doi: 10.52711/0974-360X.2022.00505 Available on: https://rjptonline.org/AbstractView.aspx?PID=2022-15-7-27
REFERENCES:
1. Hafler, D. A. Multiple Sclerosis. J. Clin. Invest. 2004, 113 (6), 788–794. https://doi.org/10.1172/JCI21357.
2. Du, C.; Xie, X. G Protein-Coupled Receptors as Therapeutic Targets for Multiple Sclerosis. Cell Res. 2012, 22 (7), 1108–1128. https://doi.org/10.1038/cr.2012.87.
3. Nylander, A.; Hafler, D. A. Multiple Sclerosis. J. Clin. Invest. 2012, 122 (4), 1180–1188. https://doi.org/10.1172/JCI58649.
4. Ghasemi, N.; Razavi, S.; Nikzad, E. Multiple Sclerosis: Pathogenesis, Symptoms, Diagnoses and Cell-Based Therapy. Cell J. Yakhteh 2017, 19 (1), 1–10.
5. Boyd, A.; Zhang, H.; Williams, A. Insufficient OPC Migration into Demyelinated Lesions Is a Cause of Poor Remyelination in MS and Mouse Models. Acta Neuropathol. (Berl.) 2013, 125 (6), 841–859. https://doi.org/10.1007/s00401-013-1112-y.
6. Hametner, S.; Wimmer, I.; Haider, L.; Pfeifenbring, S.; Brück, W.; Lassmann, H. Iron and Neurodegeneration in the Multiple Sclerosis Brain. Ann. Neurol. 2013, 74 (6), 848–861. https://doi.org/10.1002/ana.23974.
7. Kuhlmann, T.; Miron, V.; Cui, Q.; Cuo, Q.; Wegner, C.; Antel, J.; Brück, W. Differentiation Block of Oligodendroglial Progenitor Cells as a Cause for Remyelination Failure in Chronic Multiple Sclerosis. Brain J. Neurol. 2008, 131 (Pt 7), 1749–1758. https://doi.org/10.1093/brain/awn096.
8. Wolswijk, G. Oligodendrocyte Survival, Loss and Birth in Lesions of Chronic-Stage Multiple Sclerosis. Brain J. Neurol. 2000, 123 ( Pt 1), 105–115. https://doi.org/10.1093/brain/123.1.105.
9. Zrzavy, T.; Hametner, S.; Wimmer, I.; Butovsky, O.; Weiner, H. L.; Lassmann, H. Loss of “homeostatic” Microglia and Patterns of Their Activation in Active Multiple Sclerosis. Brain J. Neurol. 2017, 140 (7), 1900–1913. https://doi.org/10.1093/brain/awx113.
10. Périer, O.; Grégoire, A. Electron Microscopic Features of Multiple Sclerosis Lesions. Brain J. Neurol. 1965, 88 (5), 937–952. https://doi.org/10.1093/brain/88.5.937.
11. Prineas, J. W.; Connell, F. Remyelination in Multiple Sclerosis. Ann. Neurol. 1979, 5 (1), 22–31. https://doi.org/10.1002/ana.410050105.
12. Barnett, M. H.; Prineas, J. W. Relapsing and Remitting Multiple Sclerosis: Pathology of the Newly Forming Lesion. Ann. Neurol. 2004, 55 (4), 458–468. https://doi.org/10.1002/ana.20016.
13. Henderson, A. P. D.; Barnett, M. H.; Parratt, J. D. E.; Prineas, J. W. Multiple Sclerosis: Distribution of Inflammatory Cells in Newly Forming Lesions. Ann. Neurol. 2009, 66 (6), 739–753. https://doi.org/10.1002/ana.21800.
14. Prineas, J. W.; Parratt, J. D. E. Oligodendrocytes and the Early Multiple Sclerosis Lesion. Ann. Neurol. 2012, 72 (1), 18–31. https://doi.org/10.1002/ana.23634.
15. Stadelmann, C.; Timmler, S.; Barrantes-Freer, A.; Simons, M. Myelin in the Central Nervous System: Structure, Function, and Pathology. Physiol. Rev. 2019, 99 (3), 1381–1431. https://doi.org/10.1152/physrev.00031.2018.
16. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination - PubMed https://pubmed.ncbi.nlm.nih.gov/10852536/ (accessed Apr 20, 2021).
17. Veto, S.; Acs, P.; Bauer, J.; Lassmann, H.; Berente, Z.; Setalo, G.; Borgulya, G.; Sumegi, B.; Komoly, S.; Gallyas, F.; Illes, Z. Inhibiting Poly (ADP-Ribose) Polymerase: A Potential Therapy against Oligodendrocyte Death. Brain J. Neurol. 2010, 133 (Pt 3), 822–834. https://doi.org/10.1093/brain/awp337.
18. Marik, C.; Felts, P. A.; Bauer, J.; Lassmann, H.; Smith, K. J. Lesion Genesis in a Subset of Patients with Multiple Sclerosis: A Role for Innate Immunity? Brain J. Neurol. 2007, 130 (Pt 11), 2800–2815. https://doi.org/10.1093/brain/awm236.
19. Sánchez-Gómez; Gonzalez Fernandez; Matute, C. Adenosine and Multiple Sclerosis. Adenosine Key Link Metab. Brain Act. 2013, 435–457. https://doi.org/10.1007/978-1-4614-3903-5_21.
20. Johnston, J. B.; Silva, C.; Gonzalez, G.; Holden, J.; Warren, K. G.; Metz, L. M.; Power, C. Diminished Adenosine A1 Receptor Expression on Macrophages in Brain and Blood of Patients with Multiple Sclerosis. Ann. Neurol. 2001, 49 (5), 650–658.
21. Mayne, M.; Shepel, P. N.; Jiang, Y.; Geiger, J. D.; Power, C. Dysregulation of Adenosine A1 Receptor-Mediated Cytokine Expression in Peripheral Blood Mononuclear Cells from Multiple Sclerosis Patients. Ann. Neurol. 1999, 45 (5), 633–639. https://doi.org/10.1002/1531-8249(199905)45:5<633:aid-ana12>3.0.co;2-x.
22. Jacobson, K. A.; Gao, Z.-G. Adenosine Receptors as Therapeutic Targets. Nat. Rev. Drug Discov. 2006, 5 (3), 247–264. https://doi.org/10.1038/nrd1983.
23. Adenosine-Associated Delivery Systems https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4863639/ (accessed Feb 16, 2021).
24. Haskó, G.; Linden, J.; Cronstein, B.; Pacher, P. Adenosine Receptors: Therapeutic Aspects for Inflammatory and Immune Diseases. Nat. Rev. Drug Discov. 2008, 7 (9), 759–770. https://doi.org/10.1038/nrd2638.
25. Loma, I.; Heyman, R. Multiple Sclerosis: Pathogenesis and Treatment. Curr. Neuropharmacol. 2011, 9 (3), 409–416. https://doi.org/10.2174/157015911796557911.
26. Gandhi, R.; Laroni, A.; Weiner, H. L. Role of the Innate Immune System in the Pathogenesis of Multiple Sclerosis. J. Neuroimmunol. 2010, 221 (1–2), 7–14. https://doi.org/10.1016/j.jneuroim.2009.10.015.
27. Inoue, K.; Koizumi, S.; Tsuda, M. The Role of Nucleotides in the Neuron--Glia Communication Responsible for the Brain Functions. J. Neurochem. 2007, 102 (5), 1447–1458. https://doi.org/10.1111/j.1471-4159.2007.04824.x.
28. Apolloni, S.; Montilli, C.; Finocchi, P.; Amadio, S. Membrane Compartments and Purinergic Signalling: P2X Receptors in Neurodegenerative and Neuroinflammatory Events. FEBS J. 2009, 276 (2), 354–364. https://doi.org/10.1111/j.1742-4658.2008.06796.x.
29. Komiyama, Y.; Nakae, S.; Matsuki, T.; Nambu, A.; Ishigame, H.; Kakuta, S.; Sudo, K.; Iwakura, Y. IL-17 Plays an Important Role in the Development of Experimental Autoimmune Encephalomyelitis. J. Immunol. Baltim. Md 1950 2006, 177 (1), 566–573. https://doi.org/10.4049/jimmunol.177.1.566.
30. Alberts, B.; Johnson, A.; Lewis, J.; Raff, M.; Roberts, K.; Walter, P. T Cells and MHC Proteins. Mol. Biol. Cell 4th Ed. 2002.
31. Carrieri, P. B.; Provitera, V.; De Rosa, T.; Tartaglia, G.; Gorga, F.; Perrella, O. Profile of Cerebrospinal Fluid and Serum Cytokines in Patients with Relapsing-Remitting Multiple Sclerosis: A Correlation with Clinical Activity. Immunopharmacol. Immunotoxicol. 1998, 20 (3), 373–382. https://doi.org/10.3109/08923979809034820.
32. Monaghan, K. L.; Wan, E. C. K. The Role of Granulocyte-Macrophage Colony-Stimulating Factor in Murine Models of Multiple Sclerosis. Cells 2020, 9 (3), 611. https://doi.org/10.3390/cells9030611.
33. Dy, V.; G, K.; Pd, H.; M, B.; La, P.; P, van der V.; He, de V.; S, A.; Cd, D. GM-CSF Promotes Migration of Human Monocytes across the Blood Brain Barrier. Eur. J. Immunol. 2015, 45 (6), 1808–1819. https://doi.org/10.1002/eji.201444960.
34. Kaskow, B. J.; Baecher-Allan, C. Effector T Cells in Multiple Sclerosis. Cold Spring Harb. Perspect. Med. 2018, 8 (4). https://doi.org/10.1101/cshperspect.a029025.
35. Morandi, F.; Horenstein, A. L.; Rizzo, R.; Malavasi, F. The Role of Extracellular Adenosine Generation in the Development of Autoimmune Diseases https://www.hindawi.com/journals/mi/2018/7019398/ (accessed Jan 22, 2021). https://doi.org/10.1155/2018/7019398.
36. Gao, Z.-G.; Jacobson, K. A. Emerging Adenosine Receptor Agonists. Expert Opin. Emerg. Drugs 2007, 12 (3), 479–492. https://doi.org/10.1517/14728214.12.3.479.
37. Kaur, T.; Borse, V.; Sheth, S.; Sheehan, K.; Ghosh, S.; Tupal, S.; Jajoo, S.; Mukherjea, D.; Rybak, L. P.; Ramkumar, V. Adenosine A1 Receptor Protects Against Cisplatin Ototoxicity by Suppressing the NOX3/STAT1 Inflammatory Pathway in the Cochlea. J. Neurosci. 2016, 36 (14), 3962–3977. https://doi.org/10.1523/JNEUROSCI.3111-15.2016.