Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases
Abstract
One of the most striking hallmarks shared by various neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease (AD), and amyotrophic lateral sclerosis, is microglia-mediated neuroinflammation. Increasing evidence indicates that microglial activation in the central nervous system is heterogeneous, which can be categorized into two opposite types: M1 phenotype and M2 phenotype. Depending on the phenotypes activated, microglia can produce either cytotoxic or neuroprotective effects. In this review, we focus on the potential role of M1 and M2 microglia and the dynamic changes of M1/M2 phenotypes that are critically associated with the neurodegenerative diseases. Generally, M1 microglia predominate at the injury site at the end stage of disease, when the immunoresolution and repair process of M2 microglia are dampened. This phenotype transformation is very complicated in AD due to the phagocytosis of regionally distributed β-amyloid (Aβ) plaque and tangles that are released into the extracellular space. The endogenous stimuli including aggregated α-synuclein, mutated superoxide dismutase, Aβ, and tau oligomers exist in the milieu that may persistently activate M1 pro-inflammatory responses and finally lead to irreversible neuron loss. The changes of microglial phenotypes depend on the disease stages and severity; mastering the stage-specific switching of M1/M2 phenotypes within appropriate time windows may provide better therapeutic benefit.
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Intranasal administration of Semax over a 7-day treatment course resulted in a 25% decrease of infarct volume in the prefrontal cortex and cognitive function recovery over the long term.
“Intranasal administration of Semax over the 7-day treatment course resulted in a 25% decrease of infarct volume in the prefrontal cortex and cognitive function recovery over the long term [45,81].”
From Protective Effects of PGC-1α Activators on Ischemic Stroke in a Rat Model of Photochemically Induced Thrombosis (2021) · cites this paper as [81]
Activated microglia and an aberrant proinflammatory phenotype contribute to neuronal damage and synaptic dysfunction by releasing cytokines, reactive oxygen species, and other inflammatory mediators, which perpetuate neurodegeneration and exacerbate Alzheimer's disease progression.
“activated microglia (De Strooper and Karran, 2016) and aberrant proinflammatory phenotype contribute to neuronal damage and synaptic dysfunction by releasing cytokines, reactive oxygen species, and other inflammatory mediators, which could perpetuate neurodegeneration and exacerbate the progression of AD (Tang and Le, 2016).”
From AD-Like Neuropsychiatric Dysfunction in a Mice Model Induced by a Combination of High-Fat Diet and Intraperitoneal Injection of Streptozotocin (2024) · cites this paper as Tang and Le, 2016
Microglia adopt two distinct activation phenotypes, composed of a proinflammatory and neurotoxic classical activation (M1) phenotype by exposure to LPS and IFNγ and an anti-inflammatory and neuroprotective alternative activation (M2) phenotype following treatment with IL-4 and IL-13.
“Microglia adopt two distinct activation phenotypes, composed of a proinflammatory and neurotoxic”
From Microglia express ABI3 in the brains of Alzheimer's disease and Nasu-Hakola disease (2017) · cites this paper as [27]
The first immune response to an insult in the nervous system is the activation of microglial cells of the M2 phenotype, which is involved in anti-inflammatory mechanisms for defense and injury repair.
“The first immune response to an insult in the nervous system is the activation of microglial cells of the M2 phenotype, which is involved in anti-inflammatory mechanisms for defense and injury repair [132].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [132]
M2 microglia can release anti-inflammatory cytokines including IL-4, IL-13, IL-10, TGF-β and neurotrophic factors such as IGF-1 to assist inflammation resolution and promote neuron survival.
“These cells can release anti-inflammatory cytokines including IL-4, IL-13, IL-10, TGF-β and neurotrophic factors, such as insulin-like growth factor 1 (IGF-1) to assist inflammation resolution and promote neuron survival (Suh et al., 2013; Tang and Le, 2016).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Tang and Le, 2016
M2 microglia are the major effector cells with the potential to dampen pro-inflammatory immune responses and promote the expression of repair genes.
“M2 microglia are the major effector cells with the potential to dampen pro-inflammatory immune responses and promote the expression of repair genes (Tang and Le, 2016).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Tang and Le, 2016
Cites
Staging of brain pathology related to sporadic Parkinson’s disease
Braak, H., Tredici, K. D., Rüb, U., de Vos, R. A. I., Jansen Steur, E. N. H., & Braak, E. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00065-9 · Cited by 10,777 · see citing works
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359 · see citing works
Polazzi, E., Mengoni, I., Caprini, M., Peña‐Altamira, E., Kurtys, E., & Monti, B. (2012) · Neurosignals · doi:10.1159/000337115 · Cited by 9,023 · see citing works
Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease
Polymeropoulos, M. H., Lavedan, C., Leroy, E., Ide, S. E., Dehejia, A., Dutra, A., Pike, B., Root, H., Rubenstein, J., Boyer, R., et al. (1997) · Science · doi:10.1126/science.276.5321.2045 · Cited by 8,240 · see citing works
Alternative activation of macrophages
Gordon, S. (2003) · Nature Reviews Immunology · doi:10.1038/nri978 · Cited by 6,189 · see citing works
Dauer, W., & Przedborski, S. (2003) · Neuron · doi:10.1016/s0896-6273(03)00568-3 · Cited by 5,469 · see citing works
Obesity induces a phenotypic switch in adipose tissue macrophage polarization
Lumeng, C. N., Bodzin, J. L., & Saltiel, A. R. (2007) · Journal of Clinical Investigation · doi:10.1172/jci29881 · Cited by 4,664 · see citing works
Microglia-mediated neurotoxicity: uncovering the molecular mechanisms
Block, M. L., Zecca, L., & Hong, J.-S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2038 · Cited by 4,110 · see citing works
Microglia: Active sensor and versatile effector cells in the normal and pathologic brain
Hanisch, U.-K., & Kettenmann, H. (2007) · Nature Neuroscience · doi:10.1038/nn1997 · Cited by 3,676 · see citing works
Mechanisms underlying inflammation in neurodegeneration
Glass, C. K., Saijo, K., Winner, B., Marchetto, M. C., & Gage, F. H. (2010) · Cell · doi:10.1016/j.cell.2010.02.016 · Cited by 3,580 · see citing works
Pathways towards and Away from Alzheimer’s Disease
Mattson, M. P. (2004) · Nature · doi:10.1038/nature02621 · Cited by 3,052 · see citing works
Synapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model
Yoshiyama, Y., Higuchi, M., Zhang, B., Huang, S.-M., Iwata, N., Saido, T. C., Maeda, J., Suhara, T., Trojanowski, J. Q., & Lee, V. M.-Y. (2007) · Neuron · doi:10.1016/j.neuron.2007.01.010 · Cited by 2,208 · see citing works
Kigerl, K. A., Gensel, J. C., Ankeny, D. P., Alexander, J. K., Donnelly, D. J., & Popovich, P. G. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3257-09.2009 · Cited by 2,130 · see citing works
Macrophage-specific PPARγ controls alternative activation and improves insulin resistance
Odegaard, J. I., Ricardo-Gonzalez, R. R., Goforth, M. H., Morel, C. R., Subramanian, V., Mukundan, L., Eagle, A. R., Vats, D., Brombacher, F., Ferrante, A. W., et al. (2007) · Nature · doi:10.1038/nature05894 · Cited by 2,107 · see citing works
Decreased Clearance of CNS β-Amyloid in Alzheimer’s Disease
Mawuenyega, K. G., Sigurdson, W., Ovod, V., Munsell, L., Kasten, T., Morris, J. C., Yarasheski, K. E., & Bateman, R. J. (2010) · Science · doi:10.1126/science.1197623 · Cited by 2,078 · see citing works
Regulation of immune responses by L-arginine metabolism
Bronte, V., & Zanovello, P. (2005) · Nature Reviews Immunology · doi:10.1038/nri1668 · Cited by 1,775 · see citing works
Citron, M., Oltersdorf, T., Haass, C., McConlogue, L., Hung, A. Y., Seubert, P., Vigo-Pelfrey, C., Lieberburg, I., & Selkoe, D. J. (1992) · Nature · doi:10.1038/360672a0 · Cited by 1,757 · see citing works
The many faces of α-synuclein: from structure and toxicity to therapeutic target
Lashuel, H. A., Overk, C., Oueslati, A., & Masliah, E. (2012) · Nature reviews. Neuroscience · doi:10.1038/nrn3406 · Cited by 1,623 · see citing works
Onset and Progression in Inherited ALS Determined by Motor Neurons and Microglia
Boillée, S., Yamanaka, K., Lobsiger, C. S., Copeland, N. G., Jenkins, N. A., Kassiotis, G., Kollias, G., & Cleveland, D. W. (2006) · Science · doi:10.1126/science.1123511 · Cited by 1,623 · see citing works
Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP
Lewis, J., Dickson, D. W., Lin, W.-L., Chisholm, L., Corral, A., Jones, G., Yen, S.-H., Sahara, N., Skipper, L., Yager, D., et al. (2001) · Science · doi:10.1126/science.1058189 · Cited by 1,611 · see citing works
Microglia and inflammation-mediated neurodegeneration: Multiple triggers with a common mechanism
Block, M. L., & Hong, J.-S. (2005) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2005.06.004 · Cited by 1,557 · see citing works
ALS: A Disease of Motor Neurons and Their Nonneuronal Neighbors
Boillée, S., Velde, C. V., & Cleveland, D. W. (2006) · Neuron · doi:10.1016/j.neuron.2006.09.018 · Cited by 1,426 · see citing works
Genetics of Parkinson's DiseasePreprint
Klein, C., & Westenberger, A. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a008888 · Cited by 1,370 · see citing works
Zhang, W., Wang, T., Pei, Z., Miller, D. S., Wu, X., Block, M. L., Wilson, B., Zhang, W., Zhou, Y., Hong, J.-S., et al. (2005) · The FASEB Journal · doi:10.1096/fj.04-2751com · Cited by 1,265 · see citing works
Simard, A. R., Soulet, D., Gowing, G., Julien, J.-P., & Rivest, S. (2006) · Neuron · doi:10.1016/j.neuron.2006.01.022 · Cited by 1,265 · see citing works
Macrophage deactivation by interleukin 10.
Bogdan, C., Yoram Vodovotz, B., & Nathan, C. (1991) · The Journal of Experimental Medicine · doi:10.1084/jem.174.6.1549 · Cited by 1,236 · see citing works
In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson's disease
Gerhard, A., Pavese, N., Hotton, G., Turkheimer, F., Es, M., Hammers, A., Eggert, K., Oertel, W., Banati, R. B., & Brooks, D. J. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.08.002 · Cited by 1,200 · see citing works
Gene-expression profile of the ageing brain in mice
Lee, C.-K., Weindruch, R., & Prolla, T. A. (2000) · Nature Genetics · doi:10.1038/77046 · Cited by 1,055 · see citing works
Liberatore, G. T., Jackson-Lewis, V., Vukosavic, S., Mandir, A. S., Vila, M., McAuliffe, W. G., Dawson, V. L., Dawson, T. M., & Przedborski, S. (1999) · Nature Medicine · doi:10.1038/70978 · Cited by 1,046 · cited 1× · see citing works
“Similarly, typical characteristics of M1 phenotype including the activation of NADPH oxidase and NF-κB pathways, as well as the release of various pro-inflammatory mediators were observed in the MPTP-intoxicated models [79–81].”
BackgroundBlalock, E. M., Geddes, J. W., Chen, K. C., Porter, N. M., Markesbery, W. R., & Landfield, P. W. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308512100 · Cited by 1,025 · see citing works
Lumeng, C. N., DeYoung, S. M., Bodzin, J. L., & Saltiel, A. R. (2007) · Diabetes · doi:10.2337/db06-1076 · Cited by 1,016 · see citing works
Rapid appearance and local toxicity of amyloid-β plaques in a mouse model of Alzheimer’s disease
Meyer-Luehmann, M., Spires-Jones, T. L., Prada, C., Garcia-Alloza, M., de Calignon, A., Rozkalne, A., Koenigsknecht-Talboo, J., Holtzman, D. M., Bacskai, B. J., & Hyman, B. T. (2008) · Nature · doi:10.1038/nature06616 · Cited by 987 · see citing works
Heterogeneity of Microglial Activation in the Innate Immune Response in the Brain
Colton, C. A. (2009) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-009-9164-4 · Cited by 878 · see citing works
Polyamines in cell growth and cell death: molecular mechanisms and therapeutic applications
Thomas, T., & Thomas, T. (2001) · Cellular and Molecular Life Sciences · doi:10.1007/pl00000852 · Cited by 862 · see citing works
Microglial activation and dopamine terminal loss in early Parkinson's disease
Ouchi, Y., Yoshikawa, E., Sekine, Y., Futatsubashi, M., Kanno, T., Ogusu, T., & Torizuka, T. (2005) · Annals of Neurology · doi:10.1002/ana.20338 · Cited by 846 · see citing works
Why neurodegenerative diseases are progressive: uncontrolled inflammation drives disease progression
Gao, H., & Hong, J. (2008) · Trends in Immunology · doi:10.1016/j.it.2008.05.002 · Cited by 822 · see citing works
Minocycline selectively inhibits M1 polarization of microglia
Kobayashi, K., Imagama, S., Ohgomori, T., Hirano, K., Uchimura, K., Sakamoto, K., Hirakawa, A., Takeuchi, H., Suzumura, A., Ishiguro, N., et al. (2013) · Cell Death & Disease · doi:10.1038/cddis.2013.54 · Cited by 742 · see citing works
Beers, D. R., Henkel, J. S., Xiao, Q., Zhao, W., Wang, J., Yen, A. A., Siklos, L., McKercher, S. R., & Appel, S. H. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0607423103 · Cited by 733 · see citing works
Streit, W. J., Braak, H., Xue, Q.-S., & Bechmann, I. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0556-6 · Cited by 727 · see citing works
Hesse, M., Modolell, M., Flamme, A. C. L., Schito, M. L., Fuentes, J. M., Cheever, A. W., Pearce, E. J., & Wynn, T. A. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.11.6533 · Cited by 706 · see citing works
Buechler, C., Ritter, M., Orsó, E., Langmann, T., Klucken, J., & Schmitz, G. (2000) · Journal of Leukocyte Biology · doi:10.1002/jlb.67.1.97 · Cited by 704 · see citing works
Gao, H., Jiang, J., Wilson, B. C., Zhang, W., Hong, J., & Liu, B. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00928.x · Cited by 690 · see citing works
Proline and hydroxyproline metabolism: implications for animal and human nutrition
Wu, G., Bazer, F. W., Burghardt, R. C., Johnson, G. A., Kim, S. W., Knabe, D. A., Li, P., Li, X., McKnight, J. R., Satterfield, M. C., et al. (2010) · Amino Acids · doi:10.1007/s00726-010-0715-z · Cited by 688 · see citing works
Immune activation in brain aging and neurodegeneration: too much or too little?
Lucin, K. M., & Wyss-Coray, T. (2009) · Neuron · doi:10.1016/j.neuron.2009.08.039 · Cited by 679 · see citing works
Holcomb, I. N., Kabakoff, R. C., Chan, B., Baker, T. W., Gurney, A. L., Henzel, W. J., Nelson, C., Lowman, H. B., Wright, B. D., Skelton, N. J., et al. (2000) · The EMBO Journal · doi:10.1093/emboj/19.15.4046 · Cited by 658 · see citing works
Neuroinflammation in amyotrophic lateral sclerosis: role of glial activation in motor neuron disease
Philips, T., & Robberecht, W. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(11)70015-1 · Cited by 646 · see citing works
The mannose receptor is a pattern recognition receptor involved in host defense
Stahl, P. D., & Ezekowitz, R. A. B. (1998) · Current Opinion in Immunology · doi:10.1016/s0952-7915(98)80031-9 · Cited by 639 · see citing works
Regulation of Tau Pathology by the Microglial Fractalkine Receptor
Bhaskar, K., Konerth, M., Kokiko-Cochran, O. N., Cardona, A., Ransohoff, R. M., & Lamb, B. T. (2010) · Neuron · doi:10.1016/j.neuron.2010.08.023 · Cited by 639 · see citing works
Microglia Induce Motor Neuron Death via the Classical NF-κB Pathway in Amyotrophic Lateral Sclerosis
Frakes, A. E., Ferraiuolo, L., Haidet-Phillips, A. M., Schmelzer, L., Braun, L., Miranda, C. J., Ladner, K. J., Bevan, A. K., Foust, K. D., Godbout, J. P., et al. (2014) · Neuron · doi:10.1016/j.neuron.2014.01.013 · Cited by 638 · see citing works
Wu, D., Teismann, P., Tieu, K., Vila, M., Jackson-Lewis, V. R., Ischiropoulos, H., & Przedborski, S. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0937239100 · Cited by 634 · see citing works
Colangelo, V., Schurr, J., Ball, M. J., Pelaez, R. P., Bazan, N. G., & Lukiw, W. J. (2002) · Journal of Neuroscience Research · doi:10.1002/jnr.10351 · Cited by 517 · see citing works
Interactions of polyamines with ion channels
Williams, K. L. (1997) · Biochemical Journal · doi:10.1042/bj3250289 · Cited by 500 · see citing works
Reactive Glia not only Associates with Plaques but also Parallels Tangles in Alzheimer’s Disease
Serrano-Pozo, A., Mielke, M. L., Gómez-Isla, T., Betensky, R. A., Growdon, J. H., Frosch, M. P., & Hyman, B. T. (2011) · The American Journal of Pathology · doi:10.1016/j.ajpath.2011.05.047 · Cited by 488 · see citing works
Mannose Receptor-Mediated Regulation of Serum Glycoprotein Homeostasis
Lee, S. J., Evers, S., Röder, D., Parlow, A. F., Risteli, J., Risteli, L., Lee, Y. C., Feizi, T., Langen, H., & Nussenzweig, M. C. (2002) · Science · doi:10.1126/science.1069540 · Cited by 484 · see citing works
Koenigsknecht-Talboo, J., & Landreth, G. E. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.1808-05.2005 · Cited by 477 · see citing works
The role of extracellular matrix in CNS regeneration
Busch, S. A., & Silver, J. (2007) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2006.09.004 · Cited by 468 · see citing works
Beers, D. R., Henkel-Tigges, J., Zhao, W., Wang, J., & Appel, S. H. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0807419105 · Cited by 468 · see citing works
Hevener, A. L., Olefsky, J. M., Reichart, D., Nguyen, M. T. A., Bandyopadyhay, G., Leung, H.-Y., Watt, M. J., Benner, C., Febbraio, M. A., Nguyen, A.-K., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31561 · Cited by 459 · see citing works
The macrophage scavenger receptor CD163
Fabriek, B. O., Dijkstra, C. D., & van den Berg, T. K. (2005) · Immunobiology · doi:10.1016/j.imbio.2005.05.010 · Cited by 456 · see citing works
Differential expression of FIZZ1 and Ym1 in alternatively versus classically activated macrophages
Raes, G., BAETSELIER, P. D., Noël, W., Beschin, A., Brombacher, F., & Gh., G. H. (2002) · Journal of Leukocyte Biology · doi:10.1189/jlb.71.4.597 · Cited by 443 · see citing works
Transformation from a neuroprotective to a neurotoxic microglial phenotype in a mouse model of ALS
Liao, B., Zhao, W., Beers, D. R., Henkel-Tigges, J., & Appel, S. H. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2012.06.011 · Cited by 438 · see citing works
Neuroinflammation and Oxidation/Nitration of α-Synuclein Linked to Dopaminergic Neurodegeneration
Gao, H., Kotzbauer, P. T., Uryu, K., Leight, S., Trojanowski, J. Q., & Lee, V. M. ‐. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0143-07.2008 · Cited by 435 · see citing works
Assessing Activation States in Microglia
Colton, C. A., & Wilcock, D. M. (2010) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152710791012053 · Cited by 421 · see citing works
Michelucci, A., Heurtaux, T., Grandbarbe, L., Morga, E., & Heuschling, P. (2009) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2009.02.003 · Cited by 411 · see citing works
Expression profiles for macrophage alternative activation genes in AD and in mouse models of AD.
(2006) · Journal of Neuroinflammation · doi:10.1186/1742-2094-3-27 · Cited by 393 · see citing works
Recklies, A. D., White, C., & Ling, H. (2002) · Biochemical Journal · doi:10.1042/bj20020075 · Cited by 389 · see citing works
Butovsky, O., Koronyo-Hamaoui, M., Kunis, G., Ophir, E., Landa, G., Cohen, H., & Schwartz, M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604681103 · Cited by 388 · see citing works
Jimenez, S., Baglietto-Vargas, D., Caballero, C., Moreno-Gonzalez, I., Torres, M., Sanchez-Varo, R., Ruano, D., Vizuete, M., Gutierrez, A., & Vitorica, J. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.3024-08.2008 · Cited by 383 · cited 10× · see citing works
“seems to maintain even at relative old ages, suggesting that activated microglia surrounding Aβ plaques adopted an alternative phenotype, regardless of the age [92].”
BackgroundInfluentialNeuroprotective role of the innate immune system by microglia
Glezer, I., Simard, A. R., & Rivest, S. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.02.055 · Cited by 371 · see citing works
Chieppa, M., Bianchi, G., Doni, A., Prete, A. D., Sironi, M., Laškarin, G., Monti, P., Piemonti, L., Biondi, A., Mantovani, A., et al. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.9.4552 · Cited by 368 · see citing works
Butovsky, O., Talpalar, A. E., Ben‐Yaakov, K., & Schwartz, M. (2005) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2005.03.005 · Cited by 368 · see citing works
The mannose receptor: linking homeostasis and immunity through sugar recognition
TAYLOR, P., GORDON, S., & MARTINEZPOMARES, L. (2005) · Trends in Immunology · doi:10.1016/j.it.2004.12.001 · Cited by 368 · see citing works
Theodore, S., Cao, S., McLean, P. J., & Standaert, D. G. (2008) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31818e5e99 · Cited by 367 · see citing works
Microglia in ALS: The Good, The Bad, and The Resting
Henkel, J. S., Beers, D. R., Zhao, W., & Appel, S. H. (2009) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-009-9171-5 · Cited by 353 · see citing works
Madsen, D. H., Leonard, D., Masedunskas, A., Moyer, A. B., Jürgensen, H. J., Peters, D. E., Amornphimoltham, P., Selvaraj, A., Yamada, S. S., Brenner, D. A., et al. (2013) · The Journal of Cell Biology · doi:10.1083/jcb.201301081 · Cited by 350 · see citing works
Ponomarev, E. D., Maresz, K., Tan, Y., & Dittel, B. N. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.1922-07.2007 · Cited by 339 · see citing works
Swarup, V., Phaneuf, D., Dupré, N., Petri, S., Strong, M. J., Križ, J., & Julien, J. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20111313 · Cited by 338 · see citing works
Role of inflammation in neurodegenerative diseases
Minghetti, L. (2005) · Current Opinion in Neurology · doi:10.1097/01.wco.0000169752.54191.97 · Cited by 335 · see citing works
Chakrabarty, P., Jansen‐West, K., Beccard, A., Ceballos‐Diaz, C., Levites, Y., Verbeeck, C., Zubair, A. C., Dickson, D., Golde, T. E., & Das, P. (2010) · The FASEB Journal · doi:10.1096/fj.09-141754 · Cited by 328 · see citing works
Increased interleukin-6 expression by microglia from brain of aged mice
Ye, S.-M., & Johnson, R. W. (1999) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(98)00217-3 · Cited by 327 · see citing works
C-type lectins and phagocytosis
Kerrigan, A. M., & Brown, G. D. (2009) · Immunobiology · doi:10.1016/j.imbio.2008.11.003 · Cited by 325 · see citing works
Ding, H., & Demple, B. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.10.5146 · Cited by 313 · see citing works
Gao, H., Liu, B., Zhang, W., & Hong, J. (2003) · The FASEB Journal · doi:10.1096/fj.03-0109fje · Cited by 306 · see citing works
Maezawa, I., Zimin, P. I., Wulff, H., & Jin, L. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.135244 · Cited by 279 · see citing works
A Macrophage Protein, Ym1, Transiently Expressed during Inflammation Is a Novel Mammalian Lectin*
Chang, N., Hung, S.-I., Hwa, K., Kato, I., Chen, J.-E., Liu, C.-H., & Chang, A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010417200 · Cited by 276 · see citing works
Microglial Activation and Dopaminergic Cell Injury: AnIn VitroModel Relevant to Parkinson's Disease
Le, W. D., Rowe, D. B., Xie, W., Ortiz, I., He, Y., & Appel, S. H. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-21-08447.2001 · Cited by 274 · see citing works
Self-citationNair, M. G., Du, Y., Perrigoue, J., Zaph, C., Taylor, J. J., Goldschmidt, M. H., Swain, G. P., Yancopoulos, G. D., Valenzuela, D. M., Murphy, A. J., et al. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20082048 · Cited by 272 · see citing works
Lee, E.-J., Woo, M.-S., Moon, P., Baek, M., Choi, I.-Y., Kim, W.-K., Junn, E., & Kim, H.-S. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903480 · Cited by 267 · see citing works
Appel, S. H., Beers, D. R., & Henkel, J. S. (2010) · Trends in Immunology · doi:10.1016/j.it.2009.09.003 · Cited by 256 · see citing works
Sánchez-Guajardo, V., Barnum, C. J., Tansey, M. G., & Romero‐Ramos, M. (2013) · ASN NEURO · doi:10.1042/an20120066 · Cited by 237 · see citing works
Welch, J. S., Escoubet‐Lozach, L., Sykes, D. B., Liddiard, K., Greaves, D. R., & Glass, C. K. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205873200 · Cited by 233 · see citing works
The changing phenotype of microglia from homeostasis to disease
Luo, X., & Chen, S. (2012) · Translational Neurodegeneration · doi:10.1186/2047-9158-1-9 · Cited by 232 · see citing works
Sheng, J. G., Mrak, R. E., & Griffin, W. S. T. (1998) · Acta Neuropathologica · doi:10.1007/s004010050792 · Cited by 229 · see citing works
Suh, H.-S., Zhao, M.-L., Derico, L., Choi, N., & Lee, S. C. (2013) · Journal of Neuroinflammation · doi:10.1186/1742-2094-10-37 · Cited by 226 · see citing works
Ledeboer, A., Brev�, J. J. P., Poole, S., Tilders, F. J. H., & van Dam, A. (2000) · Glia · doi:10.1002/(sici)1098-1136(200004)30:2 · Cited by 225 · see citing works
Intrahippocampal LPS injections reduce Aβ load in APP+PS1 transgenic mice
DiCarlo, G. (2001) · Neurobiology of Aging · doi:10.1016/s0197-4580(01)00292-5 · Cited by 223 · see citing works
Sawada, M., Suzumura, A., Hosoya, H., Marunouchi, T., & Nagatsu, T. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.721466.x · Cited by 223 · see citing works
Choi, S., Aïd, S., Kim, H., Jackson, S. H., & Bosetti, F. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07572.x · Cited by 222 · see citing works
Tang, Y., Li, T., Li, J., Yang, J., Liu, H., Zhang, X.-X., & Le, W. (2013) · Cell Death and Differentiation · doi:10.1038/cdd.2013.159 · Cited by 221 · see citing works
Self-citationHensley, K. (2003) · Neurobiology of Disease · doi:10.1016/s0969-9961(03)00087-1 · Cited by 220 · see citing works
Kiyota, T., Dixie, K. L. I., Swan, R. J., Jacobsen, M. T., Andrews, S. J., & Ikezu, T. (2011) · Gene Therapy · doi:10.1038/gt.2011.126 · Cited by 216 · see citing works
Nathan, C., Calingasan, N., Nezezon, J., Ding, A., Lucia, M. S., La Perle, K., Fuortes, M., Lin, M., Ehrt, S., Kwon, N. S., et al. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20051529 · Cited by 214 · see citing works
Kiyota, T., Okuyama, S., Swan, R. J., Jacobsen, M. T., Gendelman, H. E., & Ikezu, T. (2010) · The FASEB Journal · doi:10.1096/fj.10-155317 · Cited by 212 · see citing works
Chakrabarty, P., Ceballos-Diaz, C., Beccard, A., Janus, C., Dickson, D., Golde, T. E., & Das, P. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903382 · Cited by 206 · see citing works
Li, R., Huang, Y., Du, F., & Le, W. (2004) · Journal of Neuroscience Research · doi:10.1002/jnr.20315 · Cited by 205 · see citing works
Self-citationZhang, W., Wang, T., Qin, L., Gao, H., Wilson, B. C., Ali, S. F., Zhang, W., Hong, J., & Liu, B. (2004) · The FASEB Journal · doi:10.1096/fj.03-0983fje · Cited by 204 · see citing works
Ye, S.-M., & Johnson, R. W. (2001) · Neuroimmunomodulation · doi:10.1159/000049025 · Cited by 203 · see citing works
Wilcock, D. M., Lewis, M. R., Nostrand, W. E. V., Davis, J., Previti, M. L., Gharkholonarehe, N., Vitek, M. P., & Colton, C. A. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.5066-07.2008 · Cited by 187 · see citing works
Walker, D. G., Link, J., Lue, L., Dalsing-Hernandez, J. E., & Boyes, B. E. (2005) · Journal of Leukocyte Biology · doi:10.1189/jlb.0705377 · Cited by 180 · see citing works
Modeling Parkinson's Disease in Primates: The MPTP ModelPreprint
Porras, G., Li, Q., & Bézard, E. (2011) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a009308 · Cited by 180 · see citing works
Takata, K., Kitamura, Y., Saeki, M., Terada, M., Kagitani, S., Kitamura, R., Fujikawa, Y., Maelicke, A., Tomimoto, H., Taniguchi, T., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.142356 · Cited by 176 · see citing works
Mutant SOD1<sup>G93A</sup> microglia are more neurotoxic relative to wild‐type microglia
Xiao, Q., Zhao, W., Beers, D. R., Yen, A. A., Xie, W., Henkel, J. S., & Appel, S. H. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04677.x · Cited by 174 · see citing works
Zhao, W., Xie, W., Xiao, Q., Beers, D. R., & Appel, S. H. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04172.x · Cited by 172 · see citing works
Zhang, W., Dallas, S., Zhang, D., Guo, J., Pang, H., Wilson, B. C., Miller, D. S., Chen, B., Zhang, W., McGeer, P. L., et al. (2007) · Glia · doi:10.1002/glia.20532 · Cited by 161 · see citing works
Tau Oligomers and Fibrils Induce Activation of Microglial Cells
Morales, I., Jiménez, J. M., Mancilla, M., & Maccioni, R. B. (2013) · Journal of Alzheimer’s Disease · doi:10.3233/jad-131843 · Cited by 160 · see citing works
TGFβ signalling plays an important role in IL4-induced alternative activation of microglia
Zhou, X., Spittau, B., & Krieglstein, K. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-210 · Cited by 159 · see citing works
Sugama, S., Yang, L., Cho, B. P., DeGiorgio, L. A., Lorenzl, S., Albers, D. S., Beal, M. F., Volpe, B. T., & Joh, T. H. (2003) · Brain Research · doi:10.1016/s0006-8993(02)04085-4 · Cited by 153 · see citing works
Time-dependent reduction in Aβ levels after intracranial LPS administration in APP transgenic mice
Herber, D. L., Roth, L. M., Wilson, D. H., Wilson, N., Mason, J. E., Morgan, D., & Gordon, M. N. (2004) · Experimental Neurology · doi:10.1016/j.expneurol.2004.07.007 · Cited by 147 · see citing works
Žilka, N., Kazmerova, Z., Jadhav, S., Neradil, P., Maďari, A., Obetkova, D., Bugos, O., & Novák, M. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-47 · Cited by 147 · see citing works
Redox modifier genes in amyotrophic lateral sclerosis in mice
Marden, J. J., Harraz, M. M., Williams, A. J., Nelson, K., Luo, M., Paulson, H., & Engelhardt, J. F. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31265 · Cited by 145 · see citing works
Butovsky, O., Koronyo‐Hamaoui, M., Kunis, G., Ophir, E., Landa, G., Cohen, H., & Schwartz, M. (2006) · Cited by 144 · see citing works
α-Synuclein Expression Modulates Microglial Activation Phenotype
Austin, S. A., Floden, A. M., Murphy, E. J., & Combs, C. K. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.1799-06.2006 · Cited by 142 · see citing works
Effect of 3-Hydroxyproline Residues on Collagen Stability
Jenkins, C. L., Bretscher, L. E., Guzei, I. A., et al. (2003) · Journal of the American Chemical Society · doi:10.1021/ja034015j · Cited by 141 · see citing works
Herber, D. L., Mercer, M., Roth, L. M., Symmonds, K., Maloney, J. L., Wilson, N., Freeman, M. J., Morgan, D., & Gordon, M. N. (2007) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-007-9069-z · Cited by 138 · see citing works
Ding, Y. M., Jaumotte, J. D., Signore, A. P., & Zigmond, M. J. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02415.x · Cited by 137 · see citing works
Liu, Y., Hao, W., Letièmbre, M., Walter, S., Kulanga, M., Neumann, H., & Fassbender, K. C. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.2531-06.2006 · Cited by 131 · see citing works
IL‐4 attenuates the neuroinflammation induced by amyloid‐β in vivo and in vitro
Lyons, A., Griffin, R. J., Costelloe, C., Clarke, R. M., & Lynch, M. A. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04370.x · Cited by 129 · see citing works
Nitrated Alpha-Synuclein and Microglial Neuroregulatory Activities
Reynolds, A. D., Kadiu, I., Garg, S. K., Glanzer, J. G., Nordgren, T. M., Ciborowski, P. S., Banerjee, R. V., & Gendelman, H. E. (2008) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-008-9100-z · Cited by 128 · see citing works
Increased arginase activity and endothelial dysfunction in human inflammatory bowel disease
Horowitz, S. A., Binion, D. G., Nelson, V. M., Kanaa, Y., Javadi, P., Lazarova, Z., Andrekopoulos, C., Kalyanaraman, B., Otterson, M. F., & Rafiee, P. (2007) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00499.2006 · Cited by 126 · see citing works
Accumulation of Filamentous Tau in the Cerebral Cortex of Human Tau R406W Transgenic Mice
Ikeda, M., Kawarai, T., Kawarabayashi, T., Matsubara, E., Murakami, T., Sasaki, A., Tomidokoro, Y., Ikarashi, Y., Kuribara, H., Ishiguro, K., et al. (2005) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)62274-2 · Cited by 120 · see citing works
Lee, D. C., Ruiz, C. R., Lebson, L. A., Selenica, M. B., Rizer, J., Hunt, J. B., Rojiani, R., Reid, P., Kammath, S., Nash, K. R., et al. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.12.014 · Cited by 119 · see citing works
Hippocampal expression of murine TNFα results in attenuation of amyloid deposition in vivo
Chakrabarty, P., Herring, A., Ceballos-Diaz, C., Das, P., & Golde, T. E. (2011) · Molecular Neurodegeneration · doi:10.1186/1750-1326-6-16 · Cited by 117 · see citing works
Hippocampal expression of murine IL-4 results in exacerbation of amyloid deposition
Chakrabarty, P., Tianbai, L., Herring, A., Ceballos-Diaz, C., Das, P., & Golde, T. E. (2012) · Molecular Neurodegeneration · doi:10.1186/1750-1326-7-36 · Cited by 116 · see citing works
Transforming Growth Factor-β1-Mediated Neuroprotection against Excitotoxic Injury in Vivo
Boche, D., Cunningham, C. M., Gauldie, J., & Perry, V. H. (2003) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/01.wcb.0000090080.64176.44 · Cited by 115 · see citing works
Kawahara, K., Suenobu, M., Yoshida, A., Koga, K., Hyodo, A., Ohtsuka, H., Kuniyasu, A., Tamamaki, N., Sugimoto, Y., & Nakayama, H. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.01.049 · Cited by 113 · see citing works
Recent advances in arginine metabolism
Morris, S. M. (2003) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/00075197-200401000-00009 · Cited by 107 · see citing works
Expression of mutant alpha-synuclein modulates microglial phenotype in vitro
Rojanathammanee, L., Murphy, E. J., & Combs, C. K. (2011) · Journal of Neuroinflammation · doi:10.1186/1742-2094-8-44 · Cited by 106 · see citing works
Mutant TDP-43 in motor neurons promotes the onset and progression of ALS in rats
Huang, C., Tong, J., Bi, F., Zhou, H., & Xia, X. (2011) · Journal of Clinical Investigation · doi:10.1172/jci59130 · Cited by 105 · see citing works
Wes, P. D., Easton, A. E., Corradi, J., Barten, D. M., Devidze, N., DeCarr, L. B., Truong, A. B., He, A., Barrezueta, N. X., Polson, C. T., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0106050 · Cited by 105 · see citing works
Bachstetter, A. D., Norris, C. M., Sompol, P. M., Wilcock, D. M., Goulding, D. S., Neltner, J. H., Clair, D. K. S., Watterson, D. M., & Eldik, L. J. V. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.1496-12.2012 · Cited by 105 · see citing works
Žilka, N., Stožická, Z., Kováč, A., Pilipcinec, E., Bugos, O., & Novák, M. (2009) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2009.01.013 · Cited by 98 · see citing works
Rho kinase inhibitor fasudil regulates microglia polarization and function
Zhang, H., Li, Y., Yu, J., Guo, M., Meng, J., Liu, C., Xie, Y., Feng, L., Xiao, B., & Ma, C. (2013) · Neuroimmunomodulation · doi:10.1159/000351221 · Cited by 90 · see citing works
Microglia display modest phagocytic capacity for extracellular tau oligomers
Majerova, P., Zilkova, M., Kazmerova, Z., Kovac, A., Paholikova, K., Kovacech, B., Zilka, N., & Novak, M. (2014) · Journal of Neuroinflammation · doi:10.1186/s12974-014-0161-z · Cited by 90 · see citing works
TGFβ1 regulates the inflammatory response during chronic neurodegeneration
Boche, D., Cunningham, C. M., Docagne, F., Scott, H., & Perry, V. H. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.01.004 · Cited by 89 · see citing works
Tichauer, J. E., & Rommy von Bernhardi, M. (2012) · Journal of Neuroscience Research · doi:10.1002/jnr.23082 · Cited by 88 · see citing works
Chung, W., Chang, A. C., Kato, I., & Chang, N.-C. A. (2002) · Journal of Leukocyte Biology · doi:10.1189/jlb.72.1.72 · Cited by 88 · see citing works
Neuroprotective role of microglia expressing interleukin‐4
Park, K. W., Lee, D. Y., Joe, E.-H., Kim, S. U., & Jin, B. K. (2005) · Journal of Neuroscience Research · doi:10.1002/jnr.20483 · Cited by 76 · see citing works
Sasaki, A., Kawarabayashi, T., Murakami, T., Matsubara, E., Ikeda, M., Hagiwara, H., Westaway, D. A., George‐Hyslop, P. S., Shoji, M., & Nakazato, Y. (2008) · Brain Research · doi:10.1016/j.brainres.2008.02.084 · Cited by 76 · see citing works
Lewis, K. E. A., Rasmussen, A. L., Bennett, W. R., King, A. E., West, A. K., Chung, R. S., & Chuah, M. I. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-55 · Cited by 75 · see citing works
Misfolded Truncated Protein τ Induces Innate Immune Response via MAPK Pathway
Kovac, A., Zilka, N., Kazmerova, Z., Cente, M., Zilkova, M., & Novak, M. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100216 · Cited by 75 · see citing works
Ikezu, S., & Ikezu, T. (2014) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2014.00033 · Cited by 69 · see citing works
Resistin-like molecule α enhances myeloid cell activation and promotes colitis
Munitz, A., Waddell, A., Seidu, L., Cole, E. T., Ahrens, R., Hogan, S. P., & Rothenberg, M. E. (2008) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2008.10.017 · Cited by 62 · see citing works
Asai, H., Ikezu, S., Woodbury, M. E., Yonemoto, G., Cui, L., & Ikezu, T. (2014) · American Journal Of Pathology · doi:10.1016/j.ajpath.2013.11.026 · Cited by 49 · see citing works
Resistin-Like Molecule α Decreases Glucose Tolerance during Intestinal Inflammation
Munitz, A., Seidu, L., Cole, E. T., Ahrens, R., Hogan, S. P., & Rothenberg, M. E. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0803130 · Cited by 40 · see citing works
Iribarren, P., Chen, K., Hu, J., Zhang, X., Gong, W., & Wang, J. M. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.9.6100 · Cited by 32 · see citing works
Lee, E., Yook, J.-M., Haa, K., et al. (2005) · Immunology and Cell Biology · doi:10.1111/j.1440-1711.2005.01352.x · Cited by 17 · see citing works
Kawamura, M., Yamasaki, R., Kawamura, N., Tateishi, T., Nagara, Y., Matsushita, T., Ohyagi, Y., & Kira, J. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2012.01.015 · Cited by 17 · see citing works
Tang, Y., & Le, W. (2014) · Springer eBooks · doi:10.1007/978-3-319-08046-8_4 · Cited by 9 · see citing works
Self-citationNair, M. G., Du, Y., Perrigoue, J., et al. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.2008204841009c · Cited by 7 · see citing works
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Azevedo, R. S. S., de Sousa, J. R., Araujo, M. T. F., Martins Filho, A. J., de Alcantara, B. N., Araujo, F. M. C., Queiroz, M. G. L., Cruz, A. C. R., Vasconcelos, B. H. B., Chiang, J. O., et al. (2018) · Scientific Reports · doi:10.1038/s41598-017-17765-5 · Cited by 3,478 · see citing works
Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes
Kwon, H. S., & Koh, S.-H. (2020) · Translational Neurodegeneration · doi:10.1186/s40035-020-00221-2 · Cited by 2,595 · see citing works
Microglial <scp>M1/M2</scp> polarization and metabolic states
Orihuela, R., McPherson, C. A., & Harry, G. J. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13139 · Cited by 2,070 · see citing works
Microglia in physiology and disease
Wolf, S. A., Boddeke, H. W. G. M., & Kettenmann, H. (2017) · Annual Review of Physiology · doi:10.1146/annurev-physiol-022516-034406 · Cited by 1,426 · see citing works
Wang, X., Sun, G., Feng, T., Zhang, J., Huang, X., Wang, T., Xie, Z., Chu, X., Yang, J., Wang, H., et al. (2019) · Cell Research · doi:10.1038/s41422-019-0216-x · Cited by 1,144 · see citing works
Neuroinflammation and depression: A review
Troubat, R., Barone, P., Leman, S., Desmidt, T., Cressant, A., Atanasova, B., Brizard, B., El Hage, W., Surget, A., Belzung, C., et al. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.14720 · Cited by 1,107 · see citing works
Systemic inflammation and microglial activation: systematic review of animal experiments
Hoogland, I. C. M., Houbolt, C., van Westerloo, D. J., van Gool, W. A., & van de Beek, D. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0332-6 · Cited by 957 · see citing works
Microglia polarization from M1 to M2 in neurodegenerative diseases
Guo, S., Wang, H., & Yin, Y. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.815347 · Cited by 920 · see citing works
Neuroinflammation in Parkinson's disease and its potential as therapeutic target
Wang, Q., Liu, Y., & Zhou, J. (2015) · Translational Neurodegeneration · doi:10.1186/s40035-015-0042-0 · Cited by 884 · see citing works
Microglia in Neuroinflammation and Neurodegeneration: From Understanding to Therapy
Muzio, L., Viotti, A., & Martino, G. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.742065 · Cited by 581 · see citing works
Mechanisms of Aβ Clearance and Degradation by Glial Cells
Ries, M., & Sastre, M. (2016) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2016.00160 · Cited by 527 · see citing works
“This function seems to be associated with a special and particular phenotype in microglia (formally known as M2 or alternatively activated) in contrast with the pro-inflammatory M1 state (Tang and Le, 2016).”
BackgroundDeficient autophagy in microglia impairs synaptic pruning and causes social behavioral defects
Kim, H.-J., Cho, M.-H., Shim, W. H., Kim, J. K., Jeon, E.-Y., Kim, D.-H., & Yoon, S.-Y. (2017) · Molecular Psychiatry · doi:10.1038/mp.2016.103 · Cited by 475 · see citing works
Microbiome–microglia connections via the gut–brain axis
Abdel-Haq, R., Schlachetzki, J. C. M., Glass, C. K., & Mazmanian, S. K. (2019) · Journal of Experimental Medicine · doi:10.1084/jem.20180794 · Cited by 471 · see citing works
“, nitric oxide and reactive oxygen species) into their surrounding environment to suppress and fight off invading pathogens (Franco and Fernández-Suárez, 2015; Tang and Le, 2016).”
BackgroundThe role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma.
Ramirez, A. I., de Hoz, R., Salobrar-Garcia, E., Salazar, J. J., Rojas, B., Ajoy, D., López-Cuenca, I., Rojas, P., Triviño, A., & Ramírez, J. M. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00214 · Cited by 466 · see citing works
Zhang, J., Zheng, Y., Luo, Y., Du, Y., Zhang, X., & Fu, J. (2019) · Molecular Immunology · doi:10.1016/j.molimm.2019.09.020 · Cited by 464 · see citing works
Altered Insulin Signaling in Alzheimer’s Disease Brain – Special Emphasis on PI3K-Akt Pathway
Gabbouj, S., Ryhänen, S., Marttinen, M., Wittrahm, R., Takalo, M., Kemppainen, S., Martiskainen, H., Tanila, H., Haapasalo, A., Hiltunen, M., et al. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00629 · Cited by 401 · see citing works
Microglia: Agents of the CNS Pro-Inflammatory Response
Rodríguez-Gómez, J. A., Kavanagh, E., Engskog-Vlachos, P., Engskog, M. K. R., Herrera, A. J., Espinosa-Oliva, A. M., Joseph, B., Hajji, N., Venero, J. L., & Burguillos, M. A. (2020) · Cells · doi:10.3390/cells9071717 · Cited by 365 · see citing works
A Path Toward Precision Medicine for Neuroinflammatory Mechanisms in Alzheimer's Disease
Hampel, H., Caraci, F., Cuello, A. C., Caruso, G., Nisticò, R., Corbo, M., Baldacci, F., Toschi, N., Garaci, F., Chiesa, P. A., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00456 · Cited by 360 · see citing works
“According to the phenotype activated, microglia can generate either cytotoxic or neuroprotective effects (46).”
BackgroundMicroglia Phenotypes in Aging and Neurodegenerative Diseases
Wendimu, M. Y., & Hooks, S. B. (2022) · Cells · doi:10.3390/cells11132091 · Cited by 336 · see citing works
Microglial phenotypes in Parkinson’s disease and animal models of the disease
Joers, V., Tansey, M. G., Mulas, G., & Carta, A. R. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.04.006 · Cited by 285 · see citing works
Microglia and the aging brain: are senescent microglia the key to neurodegeneration?
Angelova, D. M., & Brown, D. R. (2019) · Journal of Neurochemistry · doi:10.1111/jnc.14860 · Cited by 262 · see citing works
Sobue, A., Komine, O., Hara, Y., Endo, F., Mizoguchi, H., Watanabe, S., Murayama, S., Saito, T., Saido, T. C., Sahara, N., et al. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-01099-x · Cited by 253 · see citing works
The molecular and cellular mechanisms of depression: a focus on reward circuitry
Fox, M. E., & Lobo, M. K. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0415-3 · Cited by 232 · see citing works
Alzheimer’s disease as an inflammatory disease
Bolós, M., Perea, J. R., & Avila, J. (2017) · BioMolecular Concepts · doi:10.1515/bmc-2016-0029 · Cited by 216 · see citing works
Microglial ERK-NRBP1-CREB-BDNF Signaling in Sustained Antidepressant Actions of (R)-Ketamine
Yao, W., Cao, Q., Luo, S., He, L., Yang, C., Chen, J., Qi, Q., Hashimoto, K., & Zhang, J.-C. (2022) · Molecular Psychiatry · doi:10.1038/s41380-021-01377-7 · Cited by 217 · see citing works
Park, J.-S., Kam, T.-I., Lee, S., Park, H., Oh, Y., Kwon, S.-H., Song, J.-J., Kim, D., Kim, H., Jhaldiyal, A., et al. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01180-z · Cited by 192 · see citing works
Hamelin, L., Lagarde, J., Dorothée, G., Potier, M. C., Corlier, F., Kuhnast, B., Caillé, F., Dubois, B., Fillon, L., Chupin, M., et al. (2018) · Brain · doi:10.1093/brain/awy079 · Cited by 177 · see citing works
Zhang, C., Zhang, Y.-P., Li, Y.-Y., Liu, B.-P., Wang, H.-Y., Li, K.-W., Zhao, S., & Song, C. (2019) · Behavioural Brain Research · doi:10.1016/j.bbr.2018.07.001 · Cited by 172 · see citing works
Giacobbe, J., Benoiton, B., Zunszain, P., Pariante, C. M., & Borsini, A. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.00122 · Cited by 159 · see citing works
Inflammatory pathways in Alzheimer’s disease mediated by gut microbiota
Qian, X.-H., Song, X.-X., Liu, X.-L., Chen, S.-D., & Tang, H.-D. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101317 · Cited by 153 · see citing works
An updated assessment of microglia depletion: current concepts and future directions
Han, J., Harris, R. A., & Zhang, X.-M. (2017) · Molecular Brain · doi:10.1186/s13041-017-0307-x · Cited by 141 · see citing works
Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology
Ribeiro, D. E., Oliveira-Giacomelli, Á., Glaser, T., Arnaud-Sampaio, V. F., Andrejew, R., Dieckmann, L., Baranova, J., Lameu, C., Ratajczak, M. Z., & Ulrich, H. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-00965-3 · Cited by 145 · see citing works
Microglial priming of antigen presentation and adaptive stimulation in Alzheimer’s disease
Das, R., & Chinnathambi, S. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03132-2 · Cited by 147 · see citing works
Patricio, F., Morales-Andrade, A. A., Patricio-Martínez, A., & Limón, I. D. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.595635 · Cited by 129 · see citing works
Rangaraju, S., Raza, S. A., Li, N. X., Betarbet, R., Dammer, E. B., Duong, D., Lah, J. J., Seyfried, N. T., & Levey, A. I. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00405 · Cited by 126 · see citing works
Loss of IL-10 Promotes Differentiation of Microglia to a M1 Phenotype
Laffer, B., Bauer, D., Wasmuth, S., Busch, M., Jalilvand, T. V., Thanos, S., Meyer zu Hörste, G., Loser, K., Langmann, T., Heiligenhaus, A., et al. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00430 · Cited by 120 · see citing works
Microglia and Astrocytes in Alzheimer’s Disease: Significance and Summary of Recent Advances
Deng, Q., Wu, C., Parker, E., Liu, T. C.-Y., Duan, R., & Yang, L. (2023) · Aging and disease · doi:10.14336/ad.2023.0907 · Cited by 102 · see citing works
Neuroinflammation in Multiple System Atrophy: Response to and Cause of α-Synuclein Aggregation
Vieira, B. D. M., Radford, R. A., Chung, R. S., Guillemin, G. J., & Pountney, D. L. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00437 · Cited by 93 · see citing works
Activation of Nrf2 Pathway Contributes to Neuroprotection by the Dietary Flavonoid Tiliroside
Velagapudi, R., El-Bakoush, A., & Olajide, O. A. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-0975-2 · Cited by 91 · see citing works
The Translational Potential of Microglia and Monocyte-Derived Macrophages in Ischemic Stroke
Wicks, E. E., Ran, K. R., Kim, J. E., Xu, R., Lee, R. P., & Jackson, C. M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.897022 · Cited by 92 · see citing works
Femminella, G. D., Ninan, S., Atkinson, R., Fan, Z., Brooks, D. J., & Edison, P. (2016) · Journal of Alzheimer’s Disease · doi:10.3233/jad-150827 · Cited by 88 · see citing works
Kiyota, T., Machhi, J., Lu, Y., Dyavarshetty, B., Nemati, M., Yokoyama, I., Mosley, R. L., & Gendelman, H. E. (2018) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2018.03.009 · Cited by 80 · see citing works
Shen, Z., Bao, X., & Wang, R. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00314 · Cited by 77 · see citing works
Machado, V., Zöller, T., Attaai, A., & Spittau, B. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17020151 · Cited by 76 · see citing works
Guglielmetti, C., Le Blon, D., Santermans, E., Salas-Perdomo, A., Daans, J., De Vocht, N., Shah, D., Hoornaert, C., Praet, J., Peerlings, J., et al. (2016) · Glia · doi:10.1002/glia.23053 · Cited by 76 · see citing works
Potential Treatment of Parkinson’s Disease with Omega-3 Polyunsaturated Fatty Acids
Li, P., & Song, C. (2022) · Nutritional Neuroscience · doi:10.1080/1028415x.2020.1735143 · Cited by 74 · see citing works
Role of P2X7 Receptors in Immune Responses During Neurodegeneration
Oliveira-Giacomelli, Á., Petiz, L. L., Andrejew, R., Turrini, N., Silva, J. B., Sack, U., & Ulrich, H. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.662935 · Cited by 68 · see citing works
Untangling senescent and damage‐associated microglia in the aging and diseased brain
Ng, P. Y., McNeely, T. L., & Baker, D. J. (2023) · The FEBS Journal · doi:10.1111/febs.16315 · Cited by 68 · see citing works
Mao, R., Zhang, C., Chen, J., Zhao, G., Zhou, R., Wang, F., Xu, J., Yang, T., Su, Y., Huang, J., et al. (2018) · Journal of Affective Disorders · doi:10.1016/j.jad.2018.04.115 · Cited by 68 · see citing works
Exercise-Induced Modulation of Neuroinflammation in Models of Alzheimer’s Disease
Kelly, Á. M. (2018) · Brain Plasticity · doi:10.3233/bpl-180074 · Cited by 55 · see citing works
Microglia express ABI3 in the brains of Alzheimer's disease and Nasu-Hakola disease
Satoh, J.-I., Kino, Y., Yanaizu, M., Tosaki, Y., Sakai, K., Ishida, T., & Saito, Y. (2017) · Intractable & Rare Diseases Research · doi:10.5582/irdr.2017.01073 · Cited by 55 · see citing works
Vaz, A. R., Pinto, S., Ezequiel, C., Cunha, C., Carvalho, L. A., Moreira, R., & Brites, D. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00109 · Cited by 55 · see citing works
Zimmer, T. S., Broekaart, D. W. M., Gruber, V.-E., van Vliet, E. A., Mühlebner, A., & Aronica, E. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.01028 · Cited by 48 · see citing works
Is There Any Association Between Neurodegenerative Diseases and Periodontitis? A Systematic Review
Alvarenga, M. O. P., Frazão, D. R., Matos, I. G. D., Bittencourt, L. O., Fagundes, N. C. F., Rösing, C. K., Maia, L. C., & Lima, R. R. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.651437 · Cited by 50 · see citing works
“, 2010) via pathogenassociated molecular patterns, complement 1q, and adenosine triphosphate release from astrocytes, producing TNF-α, Il-1β, and Il-6 (Hoogland et al., 2015; Tang and Le, 2016).”
BackgroundRedefining Microglial Identity in Health and Disease at Single-Cell Resolution
Provenzano, F., Pérez, M. J., & Deleidi, M. (2021) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2020.09.001 · Cited by 45 · see citing works
Bi, W., Bao, K., Zhou, X., Deng, Y., Li, X., Zhang, J., Lan, X., Zhao, J., Lu, D., Xu, Y., et al. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02904-9 · Cited by 36 · see citing works
Kim, S. M., McIlwraith, E. K., Chalmers, J. A., & Belsham, D. D. (2018) · Neuroendocrinology · doi:10.1159/000494759 · Cited by 37 · see citing works
Absence of miRNA-146a Differentially Alters Microglia Function and Proteome
Martin, N. A., Hyrlov, K. H., Elkjaer, M. L., Thygesen, E. K., Wlodarczyk, A., Elbaek, K. J., Aboo, C., Okarmus, J., Benedikz, E., Reynolds, R., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01110 · Cited by 36 · see citing works
Uncoupling protein 2 in the glial response to stress: Implications for neuroprotection
Barnstable, C., & Hass, D. (2016) · Neural Regeneration Research · doi:10.4103/1673-5374.189159 · Cited by 33 · see citing works
Role of Glia-Derived Extracellular Vesicles in Neurodegenerative Diseases
Li, T., Tan, X., Li, S., Al-Nusaif, M., & Le, W. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.765395 · Cited by 33 · see citing works
Self-citationImmunotherapy in Glioblastoma: A Clinical Perspective
Desbaillets, N., & Hottinger, A. F. (2021) · Cancers · doi:10.3390/cancers13153721 · Cited by 31 · see citing works
Galectin-3 in Microglia-Mediated Neuroinflammation: Implications for Central Nervous System Diseases
Tian, Y.-K., Ye, D.-W., Ge, M.-M., Chen, N., Zhou, Y.-Q., & Yang, H. (2022) · Current Neuropharmacology · doi:10.2174/1570159x20666220201094547 · Cited by 31 · see citing works
miR-25-3p ameliorates SAE by targeting the TLR4/NLRP3 axis
Luo, X.-Y., Ying, J.-H., & Wang, Q.-S. (2022) · Metabolic Brain Disease · doi:10.1007/s11011-022-01017-1 · Cited by 24 · see citing works
Gu, X., Xu, L., Zheng, L., Yang, Y., Tang, Z., Wu, H., Chen, Z., & Wang, W. (2020) · IUBMB Life · doi:10.1002/iub.2353 · Cited by 21 · see citing works
Epothilone D inhibits microglia-mediated spread of alpha-synuclein aggregates
Valdinocci, D., Grant, G. D., Dickson, T. C., & Pountney, D. L. (2018) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2018.04.006 · Cited by 20 · see citing works
Panagiotakopoulou, V., Botsakis, K., Delis, F., Mourtzi, T., Tzatzarakis, M. N., Dimopoulou, A., Poulia, N., Antoniou, K., Stathopoulos, G. T., Matsokis, N., et al. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.107919 · Cited by 15 · see citing works
Liu, H.-J., Wang, M., Wang, Y., Shi, S., Hu, X., Zhang, D.-B., Fan, D., Mintzer, J., & Xu, P. (2025) · Cell Biomaterials · doi:10.1016/j.celbio.2025.100158 · Cited by 13 · see citing works
Shakova, F. M., Kirova, Y. I., Silachev, D. N., Romanova, G. A., & Morozov, S. G. (2021) · Brain Sciences · doi:10.3390/brainsci11030325 · Cited by 12 · see citing works
“Intranasal administration of Semax over the 7-day treatment course resulted in a 25% decrease of infarct volume in the prefrontal cortex and cognitive function recovery over the long term [45,81].”
BackgroundSun, H., Gao, X., Niu, J., Chen, P., He, S., Xu, S., & Ge, J. (2024) · eneuro · doi:10.1523/eneuro.0310-24.2024 · Cited by 12 · see citing works
Patel, S., Govindarajan, V., Chakravarty, S., & Dubey, N. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.113326 · Cited by 10 · see citing works
Hierarchical cortical transcriptome disorganization in autism
Lombardo, M. V., Courchesne, E., Lewis, N. E., & Pramparo, T. (2016) · doi:10.1101/042937 · Cited by 7 · see citing works
Xie, M., Wang, T., Feng, J., Ma, D., Feng, L., & Hao, Y. (2025) · Current Neuropharmacology · doi:10.2174/1570159x23666250225091729 · Cited by 7 · see citing works
- Authors
- Tang, Y., & Le, W.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Dalian Medical University (CN)
- Corresponding author
- Le, Weidong
- ORCID
- Venue
- Molecular Neurobiology
- Published
- 2015-01-20
- Volume
- 53
- Issue
- 2
- Pages
- 1181-1194
- ISSN
- 0893-7648 (ISSN-L)
- 1559-1182
- OpenAlex
- W2069893872
- Cited by
- 2,190
- References
- 159
- Citations by year
- 2026: 161 · 2025: 218 · 2024: 309 · 2023: 281 · 2022: 272 · 2021: 288 · 2020: 226 · 2019: 148 · 2018: 120 · 2017: 81 · 2016: 60 · 2015: 21
- FWCI
- 7.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Molecular Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China
- National Key Research and Development Program of China
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- microglia, M1 macrophage phenotype, M2 phenotype, neuroinflammation, neurodegenerative diseases, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, microglial polarization, amyloid plaques, tau oligomers, alpha-synuclein aggregation, neuroprotection, disease stage
- MeSH terms
- Animals, Humans, Phenotype, Microglia, Neurodegenerative Diseases
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