A Review: Metabolism of Lipid Via TREM-2A
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Abstract
This review investigated the metabolism of lipid via TREM-2. Lipid metabolism is the synthesis and degradation of lipids in cells, involving the breakdown and storage of fats for energy and the synthesis of structural and functional lipids, such as those involved in the construction of cell membranes. Lipid metabolism is often considered as the digestion and absorption process of dietary fat; however, there are two sources of fats that organisms can use to obtain energy: from consumed dietary fats and from stored fat. Triggering receptor expressed on myeloid cells 2 (TREM-2) is a membrane receptor on myeloid cells and plays an important role in the body’s immune defense. Recently, TREM-2 has received extensive attention from researchers, and its activity has been found in Alzheimer’s disease, neuroinflammation, and traumatic brain injury. The appearance of TREM-2 is usually accompanied by changes in apolipoprotein E (ApoE). Apolipoprotein E (ApoE) is a protein playing a pivotal role in lipid homeostasis since it regulates cholesterol, triglyceride and phospholipid metabolism in the blood and the brain. APOE gene regulates the expression of this protein and has three different alleles: ε2, ε3 and ε4. Carrying an APOE4 allele is recognized as a genetic risk factor of late-onset Alzheimer's disease (LOAD) and coronary heart disease (CHD). A major function of apoE is to mediate the binding of lipoproteins or lipid complexes in the plasma or interstitial fluids to specific cell-surface receptors. These receptors internalize apoE-containing lipoprotein particles; thus, apoE participates in the distribution/redistribution of lipids among various tissues and cells of the body. It is likely that apoE, with its multiple cellular origins and multiple structural and biophysical properties, is involved widely in processes of lipid metabolism and neurobiology, possibly encompassing a variety of disorders of neuronal repair, remodeling, and degeneration by interacting with different factors through various pathways.
Keywords:
Metabolism; Myeloid; Alleles; Neuroinflammation; Apolipoprotein E; Homeostasis; Phospholipid; Alzheimer; Coronary; Remodeling
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Otitoju, O., Iruka, A., & Danjuma, J. (2024). A Review: Metabolism of Lipid Via TREM-2A. Kwaghe International Journal of Sciences and Technology, 1(1), 47-63. https://doi.org/10.58578/kijst.v1i1.3398
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References
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Andreone, B. J., Przybyla, L., Llapashtica, C., Rana, A., Davis, S. S., van Lengerich, B., ... and Lewcock, J. W. (2020). Alzheimer’s-associated PLCγ2 is a signaling node required for both TREM2 function and the inflammatory response in human microglia. Nature Neuroscience, 23(8):927-938.
Atagi, Y., Liu, C. C., Painter, M. M., Chen, X. F., Verbeeck, C., Zheng, H., ... and Bu, G. (2015). Apolipoprotein E is a ligand for triggering receptor expressed on myeloid cells 2 (TREM2). Journal of Biological Chemistry, 290(43):6043-26050.
Baynes, D. (2014). Medical Biochemistry. Saunders, Elsevier Ltd. pp. 121-122.
Bouchon, A., Dietrich, J. and Colonna, M. (2000). Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes. The Journal of Immunology, 164(10):4991-4995.
Brownsey, R. W., Boone, A. N. and Elliott, J. E. (2006). Regulation of Acetyl-CoA Carboxylase. Biochemical Society Transactions, 34(2):223-227.
Cantoni, C., Bollman, B., Licastro, D., Xie, M., Mikesell, R., Schmidt, R., ... and Piccio, L. (2015). TREM2 regulates microglial cell activation in response to demyelination in vivo. Acta neuropathologica, 129: 429-447.
Chapman, N. M. and Chi, H. (2022). Metabolic adaptation of lymphocytes in immunity and disease. Immunity, 55(1): 14-30.
Chapman, N. M., Boothby, M. R., and Chi, H. (2020). Metabolic coordination of T cell quiescence and activation. Nature reviews immunology, 20(1): 55-70.
Chemistry Encyclopedia “Hydrolysis structure, reaction, water, proteins, examples, salt, molecule". chemistryexplained.com. Retrieved 2016-11-01.
Colonna, M. (2003b). TREMs in the immune system and beyond. Nature Reviews Immunology, 3(6):445–453.
Colonna, M. (2007). TREMs in the immune system and beyond. Nature Reviews Immunology, 7(6): 464–475.
Farfara, D., Trudler, D., Segev-Amzaleg, N., Galron, R., Stein, R., and Frenkel, D. (2011). γ-Secretase component presenilin is important for microglia β-amyloid clearance. Annals of Neurology, 69(1):170–180.
Feingold, K. R. and Grunfeld, C. (2000). "Introduction to Lipids and Lipoproteins". In De Groot L. J., Chrousos, G., Dungan, K., Feingold, K. R., Grossman, A., Hershman, J. M., Koch, C., Korbonits, M and McLachlan R. (eds.). Endotext. South Dartmouth (MA): MDText.com, Inc.
Fernandez, C. G., Hamby, M. E., McReynolds, M. L. and Ray, W. J. (2019). The role of APOE4 in disrupting the homeostatic functions of astrocytes and microglia in aging and Alzheimer’s disease. Frontiers in aging neuroscience, 11: 14.
Feuerbach, D., Schindler, P., Barske, C., Joller, S., Beng-Louka, E., Worringer, K. A., … Neumann, U. (2017). ADAM17 is the main sheddase for the generation of human triggering receptor expressed in myeloid cells (hTREM2) ectodomain and cleaves TREM2 after histidine 157. Neuroscience Letters, 660:109–114.
Frank, S., Burbach, G. J., Bonin, M., Walter, M., Streit, W., Bechmann, I. and Deller, T. (2008). TREM2 is upregulated in amyloid plaque-associated microglia in aged APP23 transgenic mice. Glia, 56(13):1438–1447.
Freifelder, D. (1987). Molecular biology (2nd ed.). Jones and Bartlett, Boston.
Gault, C. R., Obeid, L. M., and Hannun, Y. A. (2010). An overview of sphingolipid metabolism: from synthesis to breakdown. Sphingolipids as signaling and regulatory molecules, 1-23.
Genua, M., Rutella, S., Correale, C. and Danese, S. (2014). "The triggering receptor expressed on myeloid cells (TREM) in inflammatory bowel disease pathogenesis". Journal of Translational Medicine, 12: 293.
Harris, J. R. (Ed.). (2010). Cholesterol Binding and Cholesterol Transport Proteins:: Structure and Function in Health and Disease (Vol. 51). Springer Science and Business Media.
Jay, T. R., Hirsch, A. M., Broihier, M. L., Miller, C. M., Neilson, L. E., Ransohoff, R. M., ... and Landreth, G. E. (2017). Disease progression-dependent effects of TREM2 deficiency in a mouse model of Alzheimer's disease. Journal of Neuroscience, 37(3), 637-647.
Jay, T. R., von Saucken, V. E. and Landreth, G. E. (2017). TREM2 in neurodegenerative diseases. Molecular Neurodegeneration, 12(1):56.
Kadamur, G., and Ross, E. M. (2013). Mammalian phospholipase C. Annual review of physiology, 75(1): 127-154.
Kemmerling, N., Wunderlich, P., Theil, S., Linnartz-Gerlach, B., Hersch, N., Hoffmann, B., … Walter, J. (2017). Intramembranous processing by γ-secretase regulates reverse signaling of ephrin-B2 in migration of microglia. Glia, 65(7):1103–1118.
Kiialainen, A., Hovanes, K. and Paloneva, J. (2005). Dap12 and TREM-2, molecules involved in innate immunity and neurodegeneration, are co-expressed in the CNS. Neurobiology of Disease, 18(2):314-322.
Kleinberger, G., Yamanishi, Y., Suárez-Calvet, M., Czirr, E., Lohmann, E., Cuyvers, E., ... and Haass, C. (2014). TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis. Science translational medicine, 6(243), 243ra86-243ra86.
Klesney-Tait, J., Turnbull, I. R. and Colonna, M. (2006). The TREM receptor family and signal integration. Nature Immunology, 7(12):1266–1273.
Krasemann, S., Madore, C., Cialic, R., Baufeld, C., Calcagno, N and El Fatimy, R. (2017). The TREM-2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity, 47(3):566-81 e9.
Lehninger, A. L., Nelson, D. L. and Cox, M. M. (2000). Lehninger Principles of Biochemistry (3rd ed.). Worth Publishers, New York.
Lercher, A., Baazim, H. and Bergthaler, A. (2020). Systemic immunometabolism: challenges and opportunities. Immunity, 53:496-509.
Masuda, T., Sankowski, R., Staszewski, O. and Prinz, M (2020). "Microglia Heterogeneity in the Single-Cell Era". Cell Reports, 30 (5):1271-1281.
Nadler, Y., Alexandrovich, A., Grigoriadis, N., Hartmann, T., Rao, K. S. J., Shohami, E. and Stein, R. (2008). Increased expression of the γ-secretase components presenilin-1 and nicastrin in activated astrocytes and microglia following traumatic brain injury. Glia, 56(5):552–567.
Nugent, A. A., Lin, K., Van Lengerich, B., Lianoglou, S., Przybyla, L., Davis, S. S., ... and Di Paolo, G. (2020). TREM2 regulates microglial cholesterol metabolism upon chronic phagocytic challenge. Neuron, 105(5): 837-854.
Ophardt, C. E. (2013). Lipid Metabolism Summary. Virtual Chembook. Elmhurst College.
Paloneva, J., Manninen ,T., Christman, G., Hovanes, K., Mandelin, J. and Adolfsson, R. (2002). "Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype". American Journal of Human Genetics. 71 (3): 656-662.
Paloneva, J., Manninen, T., Christman, G., Hovanes, K., Mandelin, J., Adolfsson, R., … Peltonen, L. (2002). Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype. American Journal of Human Genetics, 71(3):656–662.
Park, J., Wetzel, I., Marriott, I., Dréau, D., D’Avanzo, C., Kim, D. Y., ... and Cho, H. (2018). A 3D human triculture system modeling neurodegeneration and neuroinflammation in Alzheimer’s disease. Nature neuroscience, 21(7):941-951.
Pelley, J. W. (2012). Elsevier's Integrated Review Biochemistry (2nd ed.). Philadelphia: Elsevier/Mosby.
Piccio, L., Buonsanti, C. and Cella, M. (2008). Identification of soluble TREM-2 in the cerebrospinal fluid and its association with multiple sclerosis and CNS inflammation. Brain, 131(11): 3081-3091.
Poliani, P. L., Wang, Y., Fontana, E., Robinette, M. L., Yamanishi, Y., Gilfillan, S. and Colonna, M. (2015). TREM2 sustains microglial expansion during aging and response to demyelination. The Journal of clinical investigation, 125(5): 2161-2170.
Prada, I., Ongania, G. N., Buonsanti, C., Panina-Bordignon, P. and Meldolesi, J. (2006). Triggering receptor expressed in myeloid cells 2 (TREM2) trafficking in microglial cells: Continuous shuttling to and from the plasmamembrane regulated by cell stimulation. Neuroscience, 140(4):1139–1148.
Schlepckow, K., Kleinberger, G., Fukumori, A., Feederle, R., Lichtenthaler, S. F., Steiner, H. and Haass, C. (2017). An Alzheimer associated TREM2 variant occurs at the ADAM cleavage site and affects shedding and phagocytic function. EMBO Molecular Medicine, 9(10):1356–1365.
Shirotani, K., Hori, Y., Yoshizaki, R., Higuchi, E., Colonna, M., Saito, T., ... and Iwata, N. (2019). Aminophospholipids are signal-transducing TREM2 ligands on apoptotic cells. Scientific Reports, 9(1): 7508.
Sudom, A., Talreja, S., Danao, J., Bragg, E., Kegel, R., Min, X., ... and Wang, Z. (2018). Molecular basis for the loss-of-function effects of the Alzheimer's disease–associated R47H variant of the immune receptor TREM2. Journal of Biological Chemistry, 293(32), 12634-12646.
Sun, H., Feng, J. and Tang, L. (2020). "Function of TREM1 and TREM-2 in Liver-Related Diseases". Cells. 9 (12):2626.
Takahashi, K, Rochford, C. D. and Neumann, H. (2005). Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed on myeloid cells-2. Journal of Experimental Medicine, 201(4):647-657.
Thornton, P., Seval__le, J., Deery, M. J., Fraser, G., Zhou, Y., Ståhl, S., … Crowther, D. C. (2017). TREM2 shedding by cleavage at the H157-S158 bond is accelerated for the Alzheimer's disease-associated H157Y variant. EMBO Molecular Medicine, 9(10):1366–1378.
Trim, W. V. and Lynch, L. (2022). Immune and non-immune functions of adipose tissue leukocytes. Nature Reviews Immunology, 22(6):371-386.
Turnbull, I. R., Gilfillan, S. and Cella, M. (2006). Cutting edge: TREM-2 attenuates macrophage activation. Journal of Immunology, 177(6):3520-3524.
Voet, D., Voet, J. G., and Pratt, C. W. (2013). Fundamentals of biochemistry: life at the molecular level. Hoboken, NJ: Wiley. pp. 581-620.
Walter, J., Kemmerling, N., Wunderlich, P. and Glebov, K. (2017). γ-Secretase in microglia - implications for neurodegeneration and neuroinflammation. Journal of Neurochemistry, 143(4):445–454.
Wculek, S. K., Dunphy, G., Heras-Murillo, I., Mastrangelo, A., and Sancho, D. (2022). Metabolism of tissue macrophages in homeostasis and pathology. Cellular and molecular immunology, 19(3):384-408.
Wunderlich, P., Glebov, K., Kemmerling, N., Tien, N. T., Neumann, H. and Walter, J. (2013). Sequential proteolytic processing of the triggering receptor expressed on myeloid cells-2 (TREM2) protein by ectodomain shedding and γ-secretase-dependent intramembranous cleavage. Journal of Biological Chemistry, 288(46):33027–33036.
Zhao, Y., Wu, X., Li, X., Jiang, L.-L., Gui, X., Liu, Y., … Xu, H. (2018). TREM2 is a receptor for β-amyloid that mediates microglial function. Neuron, 97(5):1023–1031.
Zhong, L., Wang, Z., Wang, D., Wang, Z., Martens, Y. A., Wu, L., … Chen, X.-F. (2018). Amyloid-beta modulates microglial responses by binding to the triggering receptor expressed on myeloid cells 2 (TREM2). Molecular Neurodegeneration, 13(1):15.
Andreone, B. J., Przybyla, L., Llapashtica, C., Rana, A., Davis, S. S., van Lengerich, B., ... and Lewcock, J. W. (2020). Alzheimer’s-associated PLCγ2 is a signaling node required for both TREM2 function and the inflammatory response in human microglia. Nature Neuroscience, 23(8):927-938.
Atagi, Y., Liu, C. C., Painter, M. M., Chen, X. F., Verbeeck, C., Zheng, H., ... and Bu, G. (2015). Apolipoprotein E is a ligand for triggering receptor expressed on myeloid cells 2 (TREM2). Journal of Biological Chemistry, 290(43):6043-26050.
Baynes, D. (2014). Medical Biochemistry. Saunders, Elsevier Ltd. pp. 121-122.
Bouchon, A., Dietrich, J. and Colonna, M. (2000). Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes. The Journal of Immunology, 164(10):4991-4995.
Brownsey, R. W., Boone, A. N. and Elliott, J. E. (2006). Regulation of Acetyl-CoA Carboxylase. Biochemical Society Transactions, 34(2):223-227.
Cantoni, C., Bollman, B., Licastro, D., Xie, M., Mikesell, R., Schmidt, R., ... and Piccio, L. (2015). TREM2 regulates microglial cell activation in response to demyelination in vivo. Acta neuropathologica, 129: 429-447.
Chapman, N. M. and Chi, H. (2022). Metabolic adaptation of lymphocytes in immunity and disease. Immunity, 55(1): 14-30.
Chapman, N. M., Boothby, M. R., and Chi, H. (2020). Metabolic coordination of T cell quiescence and activation. Nature reviews immunology, 20(1): 55-70.
Chemistry Encyclopedia “Hydrolysis structure, reaction, water, proteins, examples, salt, molecule". chemistryexplained.com. Retrieved 2016-11-01.
Colonna, M. (2003b). TREMs in the immune system and beyond. Nature Reviews Immunology, 3(6):445–453.
Colonna, M. (2007). TREMs in the immune system and beyond. Nature Reviews Immunology, 7(6): 464–475.
Farfara, D., Trudler, D., Segev-Amzaleg, N., Galron, R., Stein, R., and Frenkel, D. (2011). γ-Secretase component presenilin is important for microglia β-amyloid clearance. Annals of Neurology, 69(1):170–180.
Feingold, K. R. and Grunfeld, C. (2000). "Introduction to Lipids and Lipoproteins". In De Groot L. J., Chrousos, G., Dungan, K., Feingold, K. R., Grossman, A., Hershman, J. M., Koch, C., Korbonits, M and McLachlan R. (eds.). Endotext. South Dartmouth (MA): MDText.com, Inc.
Fernandez, C. G., Hamby, M. E., McReynolds, M. L. and Ray, W. J. (2019). The role of APOE4 in disrupting the homeostatic functions of astrocytes and microglia in aging and Alzheimer’s disease. Frontiers in aging neuroscience, 11: 14.
Feuerbach, D., Schindler, P., Barske, C., Joller, S., Beng-Louka, E., Worringer, K. A., … Neumann, U. (2017). ADAM17 is the main sheddase for the generation of human triggering receptor expressed in myeloid cells (hTREM2) ectodomain and cleaves TREM2 after histidine 157. Neuroscience Letters, 660:109–114.
Frank, S., Burbach, G. J., Bonin, M., Walter, M., Streit, W., Bechmann, I. and Deller, T. (2008). TREM2 is upregulated in amyloid plaque-associated microglia in aged APP23 transgenic mice. Glia, 56(13):1438–1447.
Freifelder, D. (1987). Molecular biology (2nd ed.). Jones and Bartlett, Boston.
Gault, C. R., Obeid, L. M., and Hannun, Y. A. (2010). An overview of sphingolipid metabolism: from synthesis to breakdown. Sphingolipids as signaling and regulatory molecules, 1-23.
Genua, M., Rutella, S., Correale, C. and Danese, S. (2014). "The triggering receptor expressed on myeloid cells (TREM) in inflammatory bowel disease pathogenesis". Journal of Translational Medicine, 12: 293.
Harris, J. R. (Ed.). (2010). Cholesterol Binding and Cholesterol Transport Proteins:: Structure and Function in Health and Disease (Vol. 51). Springer Science and Business Media.
Jay, T. R., Hirsch, A. M., Broihier, M. L., Miller, C. M., Neilson, L. E., Ransohoff, R. M., ... and Landreth, G. E. (2017). Disease progression-dependent effects of TREM2 deficiency in a mouse model of Alzheimer's disease. Journal of Neuroscience, 37(3), 637-647.
Jay, T. R., von Saucken, V. E. and Landreth, G. E. (2017). TREM2 in neurodegenerative diseases. Molecular Neurodegeneration, 12(1):56.
Kadamur, G., and Ross, E. M. (2013). Mammalian phospholipase C. Annual review of physiology, 75(1): 127-154.
Kemmerling, N., Wunderlich, P., Theil, S., Linnartz-Gerlach, B., Hersch, N., Hoffmann, B., … Walter, J. (2017). Intramembranous processing by γ-secretase regulates reverse signaling of ephrin-B2 in migration of microglia. Glia, 65(7):1103–1118.
Kiialainen, A., Hovanes, K. and Paloneva, J. (2005). Dap12 and TREM-2, molecules involved in innate immunity and neurodegeneration, are co-expressed in the CNS. Neurobiology of Disease, 18(2):314-322.
Kleinberger, G., Yamanishi, Y., Suárez-Calvet, M., Czirr, E., Lohmann, E., Cuyvers, E., ... and Haass, C. (2014). TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis. Science translational medicine, 6(243), 243ra86-243ra86.
Klesney-Tait, J., Turnbull, I. R. and Colonna, M. (2006). The TREM receptor family and signal integration. Nature Immunology, 7(12):1266–1273.
Krasemann, S., Madore, C., Cialic, R., Baufeld, C., Calcagno, N and El Fatimy, R. (2017). The TREM-2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity, 47(3):566-81 e9.
Lehninger, A. L., Nelson, D. L. and Cox, M. M. (2000). Lehninger Principles of Biochemistry (3rd ed.). Worth Publishers, New York.
Lercher, A., Baazim, H. and Bergthaler, A. (2020). Systemic immunometabolism: challenges and opportunities. Immunity, 53:496-509.
Masuda, T., Sankowski, R., Staszewski, O. and Prinz, M (2020). "Microglia Heterogeneity in the Single-Cell Era". Cell Reports, 30 (5):1271-1281.
Nadler, Y., Alexandrovich, A., Grigoriadis, N., Hartmann, T., Rao, K. S. J., Shohami, E. and Stein, R. (2008). Increased expression of the γ-secretase components presenilin-1 and nicastrin in activated astrocytes and microglia following traumatic brain injury. Glia, 56(5):552–567.
Nugent, A. A., Lin, K., Van Lengerich, B., Lianoglou, S., Przybyla, L., Davis, S. S., ... and Di Paolo, G. (2020). TREM2 regulates microglial cholesterol metabolism upon chronic phagocytic challenge. Neuron, 105(5): 837-854.
Ophardt, C. E. (2013). Lipid Metabolism Summary. Virtual Chembook. Elmhurst College.
Paloneva, J., Manninen ,T., Christman, G., Hovanes, K., Mandelin, J. and Adolfsson, R. (2002). "Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype". American Journal of Human Genetics. 71 (3): 656-662.
Paloneva, J., Manninen, T., Christman, G., Hovanes, K., Mandelin, J., Adolfsson, R., … Peltonen, L. (2002). Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype. American Journal of Human Genetics, 71(3):656–662.
Park, J., Wetzel, I., Marriott, I., Dréau, D., D’Avanzo, C., Kim, D. Y., ... and Cho, H. (2018). A 3D human triculture system modeling neurodegeneration and neuroinflammation in Alzheimer’s disease. Nature neuroscience, 21(7):941-951.
Pelley, J. W. (2012). Elsevier's Integrated Review Biochemistry (2nd ed.). Philadelphia: Elsevier/Mosby.
Piccio, L., Buonsanti, C. and Cella, M. (2008). Identification of soluble TREM-2 in the cerebrospinal fluid and its association with multiple sclerosis and CNS inflammation. Brain, 131(11): 3081-3091.
Poliani, P. L., Wang, Y., Fontana, E., Robinette, M. L., Yamanishi, Y., Gilfillan, S. and Colonna, M. (2015). TREM2 sustains microglial expansion during aging and response to demyelination. The Journal of clinical investigation, 125(5): 2161-2170.
Prada, I., Ongania, G. N., Buonsanti, C., Panina-Bordignon, P. and Meldolesi, J. (2006). Triggering receptor expressed in myeloid cells 2 (TREM2) trafficking in microglial cells: Continuous shuttling to and from the plasmamembrane regulated by cell stimulation. Neuroscience, 140(4):1139–1148.
Schlepckow, K., Kleinberger, G., Fukumori, A., Feederle, R., Lichtenthaler, S. F., Steiner, H. and Haass, C. (2017). An Alzheimer associated TREM2 variant occurs at the ADAM cleavage site and affects shedding and phagocytic function. EMBO Molecular Medicine, 9(10):1356–1365.
Shirotani, K., Hori, Y., Yoshizaki, R., Higuchi, E., Colonna, M., Saito, T., ... and Iwata, N. (2019). Aminophospholipids are signal-transducing TREM2 ligands on apoptotic cells. Scientific Reports, 9(1): 7508.
Sudom, A., Talreja, S., Danao, J., Bragg, E., Kegel, R., Min, X., ... and Wang, Z. (2018). Molecular basis for the loss-of-function effects of the Alzheimer's disease–associated R47H variant of the immune receptor TREM2. Journal of Biological Chemistry, 293(32), 12634-12646.
Sun, H., Feng, J. and Tang, L. (2020). "Function of TREM1 and TREM-2 in Liver-Related Diseases". Cells. 9 (12):2626.
Takahashi, K, Rochford, C. D. and Neumann, H. (2005). Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed on myeloid cells-2. Journal of Experimental Medicine, 201(4):647-657.
Thornton, P., Seval__le, J., Deery, M. J., Fraser, G., Zhou, Y., Ståhl, S., … Crowther, D. C. (2017). TREM2 shedding by cleavage at the H157-S158 bond is accelerated for the Alzheimer's disease-associated H157Y variant. EMBO Molecular Medicine, 9(10):1366–1378.
Trim, W. V. and Lynch, L. (2022). Immune and non-immune functions of adipose tissue leukocytes. Nature Reviews Immunology, 22(6):371-386.
Turnbull, I. R., Gilfillan, S. and Cella, M. (2006). Cutting edge: TREM-2 attenuates macrophage activation. Journal of Immunology, 177(6):3520-3524.
Voet, D., Voet, J. G., and Pratt, C. W. (2013). Fundamentals of biochemistry: life at the molecular level. Hoboken, NJ: Wiley. pp. 581-620.
Walter, J., Kemmerling, N., Wunderlich, P. and Glebov, K. (2017). γ-Secretase in microglia - implications for neurodegeneration and neuroinflammation. Journal of Neurochemistry, 143(4):445–454.
Wculek, S. K., Dunphy, G., Heras-Murillo, I., Mastrangelo, A., and Sancho, D. (2022). Metabolism of tissue macrophages in homeostasis and pathology. Cellular and molecular immunology, 19(3):384-408.
Wunderlich, P., Glebov, K., Kemmerling, N., Tien, N. T., Neumann, H. and Walter, J. (2013). Sequential proteolytic processing of the triggering receptor expressed on myeloid cells-2 (TREM2) protein by ectodomain shedding and γ-secretase-dependent intramembranous cleavage. Journal of Biological Chemistry, 288(46):33027–33036.
Zhao, Y., Wu, X., Li, X., Jiang, L.-L., Gui, X., Liu, Y., … Xu, H. (2018). TREM2 is a receptor for β-amyloid that mediates microglial function. Neuron, 97(5):1023–1031.
Zhong, L., Wang, Z., Wang, D., Wang, Z., Martens, Y. A., Wu, L., … Chen, X.-F. (2018). Amyloid-beta modulates microglial responses by binding to the triggering receptor expressed on myeloid cells 2 (TREM2). Molecular Neurodegeneration, 13(1):15.
