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http://dx.doi.org/10.14348/molcells.2021.0020

The Effect of Annexin A1 as a Potential New Therapeutic Target on Neuronal Damage by Activated Microglia  

You, Ji-Eun (Department of Biomedical Laboratory Science, Konyang University)
Jung, Se-Hwa (Department of Biomedical Laboratory Science, Konyang University)
Kim, Pyung-Hwan (Department of Biomedical Laboratory Science, Konyang University)
Publication Information
Molecules and Cells / v.44, no.4, 2021 , pp. 195-206 More about this Journal
Abstract
Brain disease is known to cause irrevocable and fatal loss of biological function once damaged. One of various causes of its development is damage to neuron cells caused by hyperactivated microglia, which function as immune cells in brain. Among the genes expressed in microglia stimulated by various antigens, annexin A1 (ANXA1) is expressed in the early phase of the inflammatory response and plays an important role in controlling the immune response. In this study, we assessed whether ANXA1 can be a therapeutic target gene for the initial reduction of the immune response induced by microglia to minimize neuronal damage. To address this, mouse-origin microglial cells were stimulated to mimic an immune response by lipopolysaccharide (LPS) treatment. The LPS treatment caused activation of ANXA1 gene and expression of inflammatory cytokines. To assess the biological function in microglia by the downregulation of ANXA1 gene, cells were treated with short hairpin RNA-ANXA1. Downregulated ANXA1 affected the function of mitochondria in the microglia and showed reduced neuronal damage when compared to the control group in the co-culture system. Taken together, our results showed that ANXA1 could be used as a potential therapeutic target for inflammation-related neurodegenerative diseases.
Keywords
annexin A1; brain diseases; immune response; microglia; neural damage;
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1 Colonna, M. and Butovsky, O. (2017). Microglia function in the central nervous system during health and neurodegeneration. Annu. Rev. Immunol. 35, 441-468.   DOI
2 Colton, C.A. and Wilcock, D.M. (2010). Assessing activation states in microglia. CNS Neurol. Disord. Drug Targets 9, 174-191.   DOI
3 Binder, L.I., Guillozet-Bongaarts, A.L., Garcia-Sierra, F., and Berry, R.W. (2005). Tau, tangles, and Alzheimer's disease. Biochim. Biophys. Acta 1739, 216-223.   DOI
4 Arends, Y., Duyckaerts, C., Rozemuller, J., Eikelenboom, P., and Hauw, J. (2000). Microglia, amyloid and dementia in Alzheimer disease: a correlative study. Neurobiol. Aging 21, 39-47.
5 Ashrafian, H., Zadeh, E.H., and Khan, R.H. (2020). Review on Alzheimer's disease: inhibition of amyloid beta and tau tangle formation. Int. J. Biol. Macromol. 167, 382-394.   DOI
6 Block, M.L., Zecca, L., and Hong, J.S. (2007). Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat. Rev. Neurosci. 8, 57-69.   DOI
7 Buckingham, J.C., John, C.D., Solito, E., Tierney, T., Flower, R.J., Christian, H., and Morris, J. (2006). Annexin 1, glucocorticoids, and the neuroendocrine-immune interface. Ann. N. Y. Acad. Sci. 1088, 396.   DOI
8 Chan, A., Magnus, T., and Gold, R. (2001). Phagocytosis of apoptotic inflammatory cells by microglia and modulation by different cytokines: mechanism for removal of apoptotic cells in the inflamed nervous system. Glia 33, 87-95.   DOI
9 Choi, E.J., Jeon, C.H., Park, D.H., and Kwon, T.H. (2020). Allithiamine exerts therapeutic effects on sepsis by modulating metabolic flux during dendritic cell activation. Mol. Cells 43, 964-973.   DOI
10 Nilsson, P., Iwata, N., Muramatsu, S., Tjernberg, L.O., Winblad, B., and Saido, T.C. (2010). Gene therapy in Alzheimer's disease-potential for disease modification. J. Cell. Mol. Med. 14, 741-757.   DOI
11 Nimmerjahn, A., Kirchhoff, F., and Helmchen, F. (2005). Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308, 1314-1318.   DOI
12 Magnus, T., Chan, A., Grauer, O., Toyka, K.V., and Gold, R. (2001). Microglial phagocytosis of apoptotic inflammatory T cells leads to down-regulation of microglial immune activation. J. Immunol. 167, 5004-5010.   DOI
13 Wang, N., Liang, H., and Zen, K. (2014). Molecular mechanisms that influence the macrophage M1-M2 polarization balance. Front. Immunol. 5, 614.   DOI
14 Dai, X.J., Li, N., Yu, L., Chen, Z.Y., Hua, R., Qin, X., and Zhang, Y.M. (2015). Activation of BV2 microglia by lipopolysaccharide triggers an inflammatory reaction in PC12 cell apoptosis through a toll-like receptor 4-dependent pathway. Cell Stress Chaperones 20, 321-331.   DOI
15 Jeong, S. (2017). Molecular and cellular basis of neurodegeneration in Alzheimer's disease. Mol. Cells 40, 613.   DOI
16 Katz, I.R., Jeste, D.V., Mintzer, J.E., and Clyde, C. (1999). Comparison of risperidone and placebo for psychosis and behavioral disturbances associated with dementia: a randomized, double-blind trial. J. Clin. Psychiatry 60, 107-115.   DOI
17 Lewcock, J.W., Schlepckow, K., Di Paolo, G., Tahirovic, S., Monroe, K.M., and Haass, C. (2020). Emerging microglia biology defines novel therapeutic approaches for Alzheimer's disease. Neuron 108, 801-821.   DOI
18 Liu, B. and Hong, J.S. (2003). Role of microglia in inflammation-mediated neurodegenerative diseases: mechanisms and strategies for therapeutic intervention. J. Pharmacol. Exp. Ther. 304, 1-7.   DOI
19 Ma, H.W., Ye, W., Chen, H.S., Nie, T.J., Cheng, L.F., Zhang, L., Han, P.J., Wu, X.A., Xu, Z.K., and Lei, Y.F. (2017). In-cell western assays to evaluate Hantaan virus replication as a novel approach to screen antiviral molecules and detect neutralizing antibody titers. Front. Cell. Infect. Microbiol. 7, 269.   DOI
20 Masters, C.L., Bateman, R., Blennow, K., Rowe, C.C., Sperling, R.A., and Cummings, J.L. (2015). Alzheimer's disease. Nat. Rev. Dis. Primers 1, 15056.   DOI
21 Duncan, T. and Valenzuela, M. (2017). Alzheimer's disease, dementia, and stem cell therapy. Stem Cell Res. Ther. 8, 111.   DOI
22 Pascual, O., Achour, S.B., Rostaing, P., Triller, A., and Bessis, A. (2012). Microglia activation triggers astrocyte-mediated modulation of excitatory neurotransmission. Proc. Natl. Acad. Sci. U. S. A. 109, E197-E205.   DOI
23 Perry, V.H., Nicoll, J.A., and Holmes, C. (2010). Microglia in neurodegenerative disease. Nat. Rev. Neurol. 6, 193.   DOI
24 Picca, A., Calvani, R., Coelho-Junior, H.J., Landi, F., Bernabei, R., and Marzetti, E. (2020). Mitochondrial dysfunction, oxidative stress, and neuroinflammation: intertwined roads to neurodegeneration. Antioxidants (Basel) 9, 647.   DOI
25 Davie, C.A. (2008). A review of Parkinson's disease. Br. Med. Bull. 86, 109-127.   DOI
26 Dreier, R., Schmid, K.W., Gerke, V., and Riehemann, K. (1998). Differential expression of annexins I, II and IV in human tissues: an immunohistochemical study. Histochem. Cell Biol. 110, 137-148.   DOI
27 Eikelenboom, P. and Veerhuis, R. (1996). The role of complement and activated microglia in the pathogenesis of Alzheimer's disease. Neurobiol. Aging 17, 673-680.   DOI
28 Fan, Y., Xie, L., and Chung, C.Y. (2017). Signaling pathways controlling microglia chemotaxis. Mol. Cells 40, 163.   DOI
29 Franco, R. and Fernandez-Suarez, D. (2015). Alternatively activated microglia and macrophages in the central nervous system. Prog. Neurobiol. 131, 65-86.   DOI
30 Gordon, S. and Taylor, P.R. (2005). Monocyte and macrophage heterogeneity. Nat. Rev. Immunol. 5, 953-964.   DOI
31 Graeber, M.B. (2010). Changing face of microglia. Science 330, 783-788.   DOI
32 Han, P.F., Che, X.D., Li, H.Z., Gao, Y.Y., Wei, X.C., and Li, P.C. (2020). Annexin A1 involved in the regulation of inflammation and cell signaling pathways. Chin. J. Traumatol. 23, 96-101.   DOI
33 Hanisch, U.K. and Kettenmann, H. (2007). Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat. Neurosci. 10, 1387-1394.   DOI
34 Henkel, J.S., Beers, D.R., Zhao, W., and Appel, S.H. (2009). Microglia in ALS: the good, the bad, and the resting. J. Neuroimmune Pharmacol. 4, 389-398.   DOI
35 McArthur, S., Cristante, E., Paterno, M., Christian, H., Roncaroli, F., Gillies, G.E., and Solito, E. (2010). Annexin A1: a central player in the anti-inflammatory and neuroprotective role of microglia. J. Immunol. 185, 6317-6328.   DOI
36 Qiu, X., Guo, H., Yang, J., Ji, Y., Wu, C.S., and Chen, X. (2018). Downregulation of guanylate binding protein 1 causes mitochondrial dysfunction and cellular senescence in macrophages. Sci. Rep. 8, 1-12.   DOI
37 Ramani, P.K. and Sankaran, B.P. (2020). Tay-Sachs disease. In StatPearls [Internet], B. Abai, ed. (Treasure Island: StatPearls Publishing).
38 Ransohoff, R.M. (2016). A polarizing question: do M1 and M2 microglia exist? Nat. Neurosci. 19, 987.   DOI
39 Ransohoff, R.M. and Perry, V.H. (2009). Microglial physiology: unique stimuli, specialized responses. Annu. Rev. Immunol. 27, 119-145.   DOI
40 Scheiblich, H., Trombly, M., Ramirez, A., and Heneka, M.T. (2020). Neuroimmune connections in aging and neurodegenerative diseases. Trends Immunol. 41, 300-312.   DOI
41 Shaji, K., Sivakumar, P., Rao, G.P., and Paul, N. (2018). Clinical practice guidelines for management of dementia. Indian J. Psychiatry 60(Suppl 3), S312-S328.
42 Shin, S.J., Jeon, S.G., Kim, J.I., Jeong, Y.O., Kim, S., Park, Y.H., Lee, S.K., Park, H.H., Hong, S.B., Oh, S., et al. (2019). Red ginseng attenuates Aβ-induced mitochondrial dysfunction and Aβ-mediated pathology in an animal model of Alzheimer's disease. Int. J. Mol. Sci. 20, 3030.   DOI
43 Solito, E., McArthur, S., Christian, H., Gavins, F., Buckingham, J.C., and Gillies, G.E. (2008). Annexin A1 in the brain-undiscovered roles? Trends Pharmacol. Sci. 29, 135-142.   DOI
44 Summers, W.K., Majovski, L.V., Marsh, G.M., Tachiki, K., and Kling, A. (1986). Oral tetrahydroaminoacridine in long-term treatment of senile dementia, Alzheimer type. N. Engl. J. Med. 315, 1241-1245.   DOI
45 Tang, Y. and Le, W. (2016). Differential roles of M1 and M2 microglia in neurodegenerative diseases. Mol. Neurobiol. 53, 1181-1194.   DOI