Inflammatory Response in the CNS: Friend or Foe?
Open accessAbstract
Inflammatory reactions could be both beneficial and detrimental to the brain, depending on strengths of their activation in various stages of neurodegeneration. Mild activation of microglia and astrocytes usually reveals neuroprotective effects and ameliorates early symptoms of neurodegeneration; for instance, released cytokines help maintain synaptic plasticity and modulate neuronal excitability, and stimulated toll-like receptors (TLRs) promote neurogenesis and neurite outgrowth. However, strong activation of glial cells gives rise to cytokine overexpression/dysregulation, which accelerates neurodegeneration. Altered mutual regulation of p53 protein, a major tumor suppressor, and NF-κB, the major regulator of inflammation, seems to be crucial for the shift from beneficial to detrimental effects of neuroinflammatory reactions in neurodegeneration. Therapeutic intervention in the p53-NF-κB axis and modulation of TLR activity are future challenges to cope with neurodegeneration.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In AD, brain microglial cells are activated in response to Aβ and other neuropathological changes and undergo complex neuroinflammation processes, playing either a protective or detrimental role.
“In AD, brain microglial cells are activated in response to Aβ and other neuropathological changes and undergo complex neuroinflammation processes,54 playing either a protective or detrimental role in the disease.55, 56”
From Acoustofluidic assembly of 3D neurospheroids to model Alzheimer's disease (2020) · cites this paper as [55]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Neuroinflammation in Alzheimer's disease
Heneka, M. T., Carson, M. J., Khoury, J. E., Landreth, G. E., Brosseron, F., Feinstein, D. L., Jacobs, A. H., Wyss-Coray, T., Vitorica, J., Ransohoff, R. M., et al. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)70016-5 · Cited by 6,226 · see citing works
Alternative activation of macrophages: mechanism and functions
Gordon, S., & Martinez, F. O. (2010) · Immunity · doi:10.1016/j.immuni.2010.05.007 · Cited by 4,197 · see citing works
Franceschi, C., Capri, M., Monti, D., Giunta, S., Olivieri, F., Sevini, F., Panourgia, M. P., Invidia, L., Celani, L., Scurti, M., et al. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.11.016 · Cited by 2,087 · see citing works
Neuroinflammation and M2 Microglia: The Good, the Bad, and the Inflamed
Cherry, J. D., Olschowka, J. A., & O’Banion, M. K. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-98 · Cited by 1,748 · see citing works
Neuroinflammation: The Devil Is in the Details
DiSabato, D. J., Quan, N., & Godbout, J. P. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13607 · Cited by 1,640 · see citing works
Innate immune activation in neurodegenerative disease
Heneka, M. T., Kummer, M. P., & Latz, E. (2014) · Nature Reviews Immunology · doi:10.1038/nri3705 · Cited by 1,437 · see citing works
Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease
Prinz, M., & Priller, J. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3722 · Cited by 1,329 · see citing works
Age-dependent dysregulation of innate immunity
Shaw, A. C., Goldstein, D. R., & Montgomery, R. R. (2013) · Nature Reviews Immunology · doi:10.1038/nri3547 · Cited by 1,061 · see citing works
Microglial Activation and Chronic Neurodegeneration
Lull, M. E., & Block, M. L. (2010) · Neurotherapeutics · doi:10.1016/j.nurt.2010.05.014 · Cited by 1,047 · see citing works
Origin and differentiation of microglia
Ginhoux, F., Lim, S., Hoeffel, G., Low, D., & Huber, T. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00045 · Cited by 905 · cited 1× · see citing works
“Recent investigations show fundamental roles for microglia in the control of neuronal proliferation and differentiation, as well as in the formation of synaptic connections [27, 45, 46].”
BackgroundMicroglia: Dynamic Mediators of Synapse Development and Plasticity
Wu, Y., Dissing-Olesen, L., MacVicar, B. A., & Stevens, B. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.08.008 · Cited by 661 · see citing works
Walsh, J. G., Muruve, D. A., & Power, C. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3638 · Cited by 637 · cited 3× · see citing works
“Inflammasomes generally have three main components: a cytosolic PRR (which is a member of the NLR family of protein or pyrin and the HIN domain-containing family of proteins (PYHIN)), the enzyme caspase 1, and an adaptor protein that facilitates an interaction between the two [31].”
BackgroundInfluentialHamelin, L., Lagarde, J., Dorothée, G., Leroy, C., Labit, M., Comley, R. A., de Souza, L. C., Corne, H., Dauphinot, L., Bertoux, M., et al. (2016) · Brain · doi:10.1093/brain/aww017 · Cited by 519 · see citing works
MicroRNAs in the p53 network: micromanagement of tumour suppression
Hermeking, H. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3318 · Cited by 518 · see citing works
Edison, P., Archer, H. A., Gerhard, A., Hinz, R., Pavese, N., Turkheimer, F. E., Hammers, A., Tai, Y. F., Fox, N., Kennedy, A., et al. (2008) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.08.001 · Cited by 513 · see citing works
Morales, I., Guzmán-MartÃnez, L., Cerda-Troncoso, C., FarÃas, G. A., & Maccioni, R. B. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00112 · Cited by 490 · see citing works
Contribution of inflammatory processes to Alzheimer's disease: molecular mechanisms
Sastre, M., Klockgether, T., & Heneka, M. T. (2006) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2005.11.014 · Cited by 426 · see citing works
Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity
Palmer, A. K., Tchkonia, T., LeBrasseur, N. K., Chini, E. N., Xu, M., & Kirkland, J. L. (2015) · Diabetes · doi:10.2337/db14-1820 · Cited by 423 · see citing works
Lucin, K. M., O’Brien, C. E., Bieri, G., Czirr, E., Mosher, K. I., Abbey, R. J., Mastroeni, D. F., Rogers, J., Spencer, B., Masliah, E., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.06.046 · Cited by 374 · see citing works
Il10 Deficiency Rebalances Innate Immunity to Mitigate Alzheimer-Like Pathology
Guillot-Sestier, M.-V., Doty, K. R., Gate, D., Rodriguez, J., Leung, B. P., Rezai-Zadeh, K., & Town, T. (2015) · Neuron · doi:10.1016/j.neuron.2014.12.068 · Cited by 363 · see citing works
Schwartz, M., & Baruch, K. (2014) · The EMBO Journal · doi:10.1002/embj.201386609 · Cited by 349 · see citing works
Dealing with danger in the CNS: the response of the immune system to injury
Gadani, S. P., Walsh, J. T., Lukens, J. R., & Kipnis, J. (2015) · Neuron · doi:10.1016/j.neuron.2015.05.019 · Cited by 342 · see citing works
Microglial genes regulating neuroinflammation in the progression of Alzheimer's disease
Villegas-Llerena, C., Phillips, A., Garcia-Reitboeck, P., Hardy, J., & Pocock, J. M. (2016) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2015.10.004 · Cited by 270 · see citing works
Neuroinflammation and neurodegeneration in overnutrition-induced diseases
Cai, D. (2013) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2012.11.003 · Cited by 256 · see citing works
Griffin, W. S. T., & Mrak, R. E. (2002) · Journal of Leukocyte Biology · doi:10.1189/jlb.72.2.233 · Cited by 248 · see citing works
p53, ROS and senescence in the control of aging
Vigneron, A., & Vousden, K. H. (2010) · Aging · doi:10.18632/aging.100189 · Cited by 221 · see citing works
miR‐155 as a multiple sclerosis–relevant regulator of myeloid cell polarization
Moore, C. S., Rao, V. T. S., Durafourt, B. A., Bedell, B. J., Ludwin, S. K., Bar‐Or, A., & Antel, J. P. (2013) · Annals of Neurology · doi:10.1002/ana.23967 · Cited by 219 · cited 1× · see citing works
“sponses in both blood-derived and central nervous system (CNS)-resident myeloid cells [85].”
BackgroundLeszek, J., E. Barreto, G., G|siorowski, K., Koutsouraki, E., Ávila-Rodrigues, M., & Aliev, G. (2016) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527315666160202125914 · Cited by 206 · cited 1× · see citing works
“The long-drawn release of pro-inflammatory mediators propels the inflammatory cycle by increased microglial activation and proliferation, thus stimulating enhanced release of pro-inflammatory agents [75].”
BackgroundSelf-citationImmune Surveillance of the CNS following Infection and Injury
Russo, M. V., & McGavern, D. B. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.08.002 · Cited by 191 · see citing works
TREM2 modifies microglial phenotype and provides neuroprotection in P301S tau transgenic mice
Jiang, T., Zhang, Y.-D., Chen, Q., Gao, Q., Zhu, X.-C., Zhou, J.-S., Shi, J.-Q., Lu, H., Tan, L., & Yu, J.-T. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.01.028 · Cited by 176 · see citing works
TREM2 in CNS homeostasis and neurodegenerative disease
Painter, M. M., Atagi, Y., Liu, C.-C., Rademakers, R., Xu, H., Fryer, J. D., & Bu, G. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0040-9 · Cited by 169 · see citing works
TREM2 Function in Alzheimer’s Disease and Neurodegeneration
Ulrich, J. D., & Holtzman, D. M. (2016) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.5b00313 · Cited by 154 · see citing works
Doi, Y., Mizuno, T., Maki, Y., Jin, S., Mizoguchi, H., Ikeyama, M., Doi, M., Michikawa, M., Takeuchi, H., & Suzumura, A. (2009) · The American Journal of Pathology · doi:10.2353/ajpath.2009.090418 · Cited by 135 · see citing works
Weltevrede, M., Eilers, R., de Melker, H. E., & van Baarle, D. (2016) · Experimental Gerontology · doi:10.1016/j.exger.2016.02.005 · Cited by 128 · see citing works
Microglial diversity by responses and responders
Gertig, U., & Hanisch, U.-K. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00101 · Cited by 123 · see citing works
Deciphering Resting Microglial Morphology and Process Motility from a Synaptic Prospect
Hristovska, I., & Pascual, O. (2016) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2015.00073 · Cited by 92 · see citing works
The innate immune system in Alzheimer's disease
Boutajangout, A., & Wisniewski, T. (2013) · International Journal of Cell Biology · doi:10.1155/2013/576383 · Cited by 69 · see citing works
TREM2 enables amyloid β clearance by microglia.
Rivest, S. (2015) · Cell Research · doi:10.1038/cr.2015.37 · Cited by 34 · see citing works
IL-3 Control Tau Modifications and Protects Cortical Neurons from Neurodegeneration
Zambrano, A., Otth, C., B. Maccioni, R., & I. Concha, I. (2010) · Current Alzheimer Research · doi:10.2174/156720510793499011 · Cited by 29 · see citing works
Flagged first, then by citations
Research works printed but not linked: 139
- [1]Diack AB, Alibhai JD, Barron R, Bradford B, Piccardo P, Manson JC (2016) Insights into mechanisms of chronic neurodegeneration. Int J Mol Sci 17(1) PMC4730326 26771599
- [2]Chen W-W Zhang X Huang W-J Role of neuroinflammation in neurodegenerative diseases (review) Mol Med Rep 2016 13 3391 3396 26935478 PMC4805095
- [3]Kohan R Cismondi IA Oller-Ramirez AM Guelbert N Anzolini TV Alonso G Therapeutic approaches to the challenge of neuronal ceroid lipofuscinoses Curr Pharm Biotechnol 2011 12 867 883 21235444 PMC3632406
- [5]Waisman A Liblau RS Becher B Innate and adaptive immune responses in the CNS Lancet Neurol 2015 14 945 955 26293566
- [6]Headland SE Norling LV The resolution of inflammation: principles and challenges Semin Immunol 2015 27 149 160 25911383
- [7]Całkosiński I Dobrzyński M Całkosińska M Seweryn E Bronowicka-Szydełko A Characterization of an inflammatory response Post Hig Med Dosw 2009 63 395 408 19745226
- [8]Franceschi C Campisi J Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases J Gerontol A Biol Sci Med Sci 2014 69 Suppl 1 S4 S9 24833586
- [9]Maskrey BH Megson IL Whitfield PD Rossi AG Mechanisms of resolution of inflammation: a focus on cardiovascular disease Arterioscler Thromb Vasc Biol 2011 31 1001 1006 21508346
- [12]Salvioli S Capri M Valensin S Tieri P Monti D Ottaviani E Inflamm-aging, cytokines and aging: state of the art, new hypotheses on the role of mitochondria and new perspectives from systems biology Curr Pharm Des 2006 12 3161 3171 16918441
- [13]Batra A Siegmund B The role of visceral fat Dig Dis 2012 30 70 74 22572689
- [16]Kim S-H Chung J Song S-W Jung WS Lee Y-A Kim H-N Relationship between deep subcutaneous abdominal adipose tissue and metabolic syndrome: a case control study Diabetol Metab Syndr 2016 8 10 26877772 PMC4751727
- [17]Kiliaan AJ Arnoldussen IAC Gustafson DR Adipokines: a link between obesity and dementia? Lancet Neurol 2014 13 913 923 25142458 PMC4228955
- [18]Li X Song D Leng SX Link between type 2 diabetes and Alzheimer’s disease: from epidemiology to mechanism and treatment Clin Interv Aging 2015 10 549 560 25792818 PMC4360697
- [19]van Dijk G van Heijningen S Reijne AC Nyakas C van der Zee EA Eisel ULM Integrative neurobiology of metabolic diseases, neuroinflammation, and neurodegeneration Front Neurosci 2015 9 173 26041981 PMC4434977
- [20]Kim B Feldman EL Insulin resistance as a key link for the increased risk of cognitive impairment in the metabolic syndrome Exp Mol Med 2015 47 e149 25766618 PMC4351418
- [22]Bauer ME, Fuente MD la (2016) The role of oxidative and inflammatory stress and persistent viral infections in immunosenescence. Mech Ageing Dev 7 26773975
- [23]Nasi M Pinti M De Biasi S Gibellini L Ferraro D Mussini C Aging with HIV infection: a journey to the center of inflammAIDS, immunosenescence and neuroHIV Immunol Lett 2014 162 1 Pt B 329 333 24996041
- [24]Sansoni P Vescovini R Fagnoni F Biasini C Zanni F Zanlari L The immune system in extreme longevity Exp Gerontol 2008 43 61 65 17870272
- [25]Johnson RW Alvarez-Pasquin M-J Bijl M Franco E Gaillat J Clara JG Herpes zoster epidemiology, management, and disease and economic burden in Europe: a multidisciplinary perspective Ther Adv Vaccines 2015 3 109 120 26478818 PMC4591524
- [28]Lim SL Rodriguez-Ortiz CJ Kitazawa M Infection, systemic inflammation, and Alzheimer’s disease Microbes Infect 2015 17 549 556 25912134
- [32]Barichello T Generoso JS Goularte JA Collodel A Pitcher MR Simões LR Does infection-induced immune activation contribute to dementia? Aging Dis 2015 6 342 348 26425389 PMC4567217
- [33]Khandelwal PJ Herman AM Moussa CE-H Inflammation in the early stages of neurodegenerative pathology J Neuroimmunol 2011 238 1 11 21820744 PMC3176984
- [34]Tarr AJ Liu X Reed NS Quan N Kinetic characteristics of euflammation: the induction of controlled inflammation without overt sickness behavior Brain Behav Immun 2014 42 96 108 24929192 PMC4254289
- [35]Liu X Nemeth DP Tarr AJ Belevych N Syed ZW Wang Y Euflammation attenuates peripheral inflammation-induced neuroinflammation and mitigates immune-to-brain signaling Brain Behav Immun 2016 54 140 148 26812118 PMC4828265
- [36]González H Pacheco R T-cell-mediated regulation of neuroinflammation involved in neurodegenerative diseases J Neuroinflammation 2014 11 201 25441979 PMC4258012
- [37]Lun MP Monuki ES Lehtinen MK Development and functions of the choroid plexus-cerebrospinal fluid system Nat Rev Neurosci 2015 16 445 457 26174708 PMC4629451
- [38]Schwartz M Shechter R Protective autoimmunity functions by intracranial immunosurveillance to support the mind: the missing link between health and disease Mol Psychiatry 2010 15 342 354 20332793
- [39]Schwartz M Raposo C Protective autoimmunity: a unifying model for the immune network involved in CNS repair Neurosci Rev J Bringing Neurobiol Neurol Psychiatry 2014 20 343 358 24395337
- [40]Rezaie P Male D Mesoglia & microglia—a historical review of the concept of mononuclear phagocytes within the central nervous system J Hist Neurosci 2002 11 325 374 12557654
- [41]Ginhoux F Prinz M Origin of microglia: current concepts and past controversies Cold Spring Harb Perspect Biol 2015 7 a020537 26134003 PMC4526747
- [43]Correale J The role of microglial activation in disease progression Mult Scler Houndmills Basingstoke Engl 2014 20 1288 1295 24812046
- [44]Hernandez-Ontiveros DG Tajiri N Acosta S Giunta B Tan J Borlongan CV Microglia activation as a biomarker for traumatic brain injury Front Neurol 2013 4 30 23531681 PMC3607801
- [46]Nayak D Roth TL McGavern DB Microglia development and function Annu Rev Immunol 2014 32 367 402 24471431 PMC5001846
- [48]Neumann H Kotter MR Franklin RJM Debris clearance by microglia: an essential link between degeneration and regeneration Brain J Neurol 2009 132 288 295 PMC2640215 18567623
- [49]Bahrini I Song J Diez D Hanayama R Neuronal exosomes facilitate synaptic pruning by up-regulating complement factors in microglia Sci Rep 2015 5 7989 25612542 PMC4303875
- [50]Bátiz LF Castro MA Burgos PV Velásquez ZD Muñoz RI Lafourcade CA Exosomes as novel regulators of adult neurogenic niches Front Cell Neurosci 2015 9 501 26834560 PMC4717294
- [51]Pegtel DM, Peferoen L, Amor S (2014) Extracellular vesicles as modulators of cell-to-cell communication in the healthy and diseased brain. Philos Trans R Soc Lond B Biol Sci 369(1652) PMC4142037 25135977
- [52]Frühbeis C Fröhlich D Kuo WP Amphornrat J Thilemann S Saab AS Neurotransmitter-triggered transfer of exosomes mediates oligodendrocyte-neuron communication PLoS Biol 2013 11 e1001604 23874151 PMC3706306
- [53]Bellingham SA Guo BB Coleman BM Hill AF Exosomes: vehicles for the transfer of toxic proteins associated with neurodegenerative diseases? Front Physiol 2012 3 124 22563321 PMC3342525
- [54]Turola E Furlan R Bianco F Matteoli M Verderio C Microglial microvesicle secretion and intercellular signaling Front Physiol 2012 3 149 22661954 PMC3357554
- [55]Properzi F Logozzi M Fais S Exosomes: the future of biomarkers in medicine Biomark Med 2013 7 769 778 24044569
- [56]Wang X Zhao L Zhang J Fariss RN Ma W Kretschmer F Requirement for microglia for the maintenance of synaptic function and integrity in the mature retina J Neurosci 2016 36 2827 2842 26937019 PMC4879218
- [58]Wyss-Coray T Rogers J Inflammation in Alzheimer disease—a brief review of the basic science and clinical literature Cold Spring Harb Perspect Med 2012 2 a006346 22315714 PMC3253025
- [59]Streit WJ Xue Q-S Life and death of microglia J Neuroimmune Pharmacol Off J Soc NeuroImmune Pharmacol 2009 4 371 379 19680817
- [60]Luo X-G Chen S-D The changing phenotype of microglia from homeostasis to disease Transl Neurodegener 2012 1 9 23210447 PMC3514090
- [61]von Bernhardi R Eugenín-von Bernhardi L Eugenín J Microglial cell dysregulation in brain aging and neurodegeneration Front Aging Neurosci 2015 7 124 26257642 PMC4507468
- [62]Lynch MA The impact of neuroimmune changes on development of amyloid pathology; relevance to Alzheimer’s disease Immunology 2014 141 292 301 23876085 PMC3930368
- [63]Colton CA Heterogeneity of microglial activation in the innate immune response in the brain J Neuroimmune Pharmacol Off J Soc NeuroImmune Pharmacol 2009 4 399 418 PMC2773116 19655259
- [64]Walker DG Lue L-F Immune phenotypes of microglia in human neurodegenerative disease: challenges to detecting microglial polarization in human brains Alzheimers Res Ther 2015 7 56 26286145 PMC4543480
- [65]Cappellano G Carecchio M Fleetwood T Magistrelli L Cantello R Dianzani U Immunity and inflammation in neurodegenerative diseases Am J Neurodegener Dis 2013 2 89 107 23844334 PMC3703122
- [67]Ferrini F De Koninck Y Microglia control neuronal network excitability via BDNF signalling Neural Plast 2013 2013 429815 24089642 PMC3780625
- [68]Alboni S Maggi L Editorial: cytokines as players of neuronal plasticity and sensitivity to environment in healthy and pathological brain Front Cell Neurosci 2015 9 508 26793060 PMC4709412
- [69]Sajja VSSS Hlavac N VandeVord PJ Role of glia in memory deficits following traumatic brain injury: biomarkers of glia dysfunction Front Integr Neurosci 2016 10 7 26973475 PMC4770450
- [70]Camara ML Corrigan F Jaehne EJ Jawahar MC Anscomb H Koerner H TNF-α and its receptors modulate complex behaviours and neurotrophins in transgenic mice Psychoneuroendocrinology 2013 38 3102 3114 24094876
- [71]Steinmetz CC Turrigiano GG Tumor necrosis factor-α signaling maintains the ability of cortical synapses to express synaptic scaling J Neurosci 2010 30 14685 14690 21048125 PMC3063078
- [74]Block ML Hong J-S Chronic microglial activation and progressive dopaminergic neurotoxicity Biochem Soc Trans 2007 35 1127 1132 17956294
- [76]Fischer R Maier O Interrelation of oxidative stress and inflammation in neurodegenerative disease: role of TNF Oxidative Med Cell Longev 2015 2015 610813 PMC4365363 25834699
- [77]Sochocka M Koutsouraki ES Gasiorowski K Leszek J Vascular oxidative stress and mitochondrial failure in the pathobiology of Alzheimer’s disease: a new approach to therapy CNS Neurol Disord Drug Targets 2013 12 870 881 23469836
- [78]Wu Z Yu J Zhu A Nakanishi H Nutrients, microglia aging, and brain aging Oxidative Med Cell Longev 2016 2016 7498528 PMC4752989 26941889
- [79]Varnum MM Ikezu T The classification of microglial activation phenotypes on neurodegeneration and regeneration in Alzheimer’s disease brain Arch Immunol Ther Exp 2012 60 251 266 PMC4429536 22710659
- [80]Yu Z Sun D Feng J Tan W Fang X Zhao M MSX3 switches microglia polarization and protects from inflammation-induced demyelination J Neurosci 2015 35 6350 6365 25904788 PMC6605213
- [82]Cerbai F Lana D Nosi D Petkova-Kirova P Zecchi S Brothers HM The neuron-astrocyte-microglia triad in normal brain ageing and in a model of neuroinflammation in the rat hippocampus PLoS One 2012 7 e45250 23028880 PMC3445467
- [83]McGeer PL McGeer EG Targeting microglia for the treatment of Alzheimer’s disease Expert Opin Ther Targets 2015 19 497 506 25435348
- [84]Latta CH Brothers HM Wilcock DM Neuroinflammation in Alzheimer’s disease; a source of heterogeneity and target for personalized therapy Neuroscience 2015 302 103 111 25286385 PMC4602369
- [86]Hamzei Taj S Kho W Riou A Wiedermann D Hoehn M MiRNA-124 induces neuroprotection and functional improvement after focal cerebral ischemia Biomaterials 2016 91 151 165 27031810
- [87]Ponomarev ED Veremeyko T Weiner HL MicroRNAs are universal regulators of differentiation, activation, and polarization of microglia and macrophages in normal and diseased CNS Glia 2013 61 91 103 22653784 PMC3434289
- [88]Magistretti PJ, Ransom BR (2002) Astrocytes. Neuropsychopharmacology: the fifth generation of progress. In: Davis KL, Charney D, Coyle JT, Nemeroff C (eds). Williams and Wilkins, Philadelphia, Lippincott, pp 133–145
- [89]Steardo L Bronzuoli MR Iacomino A Esposito G Steardo L Scuderi C Does neuroinflammation turn on the flame in Alzheimer’s disease? Focus on astrocytes Front Neurosci 2015 9 259 26283900 PMC4518161
- [90]Messing A Brenner M GFAP: functional implications gleaned from studies of genetically engineered mice Glia 2003 43 87 90 12761871
- [91]Tanaka KF Takebayashi H Yamazaki Y Ono K Naruse M Iwasato T Murine model of Alexander disease: analysis of GFAP aggregate formation and its pathological significance Glia 2007 55 617 631 17299771
- [92]Mohn TC Koob AO Adult astrogenesis and the etiology of cortical neurodegeneration J Exp Neurosci 2015 9 Suppl 2 25 34 26568684 PMC4634839
- [93]Fuller S Steele M Münch G Activated astroglia during chronic inflammation in Alzheimer’s disease—do they neglect their neurosupportive roles? Mutat Res 2010 690 40 49 19748514
- [94]Zhao J O’Connor T Vassar R The contribution of activated astrocytes to Aβ production: implications for Alzheimer’s disease pathogenesis J Neuroinflammation 2011 8 150 22047170 PMC3216000
- [95]Efremova L, Chovancova P, Adam M, Gutbier S, Schildknecht S, Leist M (2016) Switching from astrocytic neuroprotection to neurodegeneration by cytokine stimulation. Arch Toxicol Apr 6 27052459
- [98]Salminen A Ojala J Suuronen T Kaarniranta K Kauppinen A Amyloid-beta oligomers set fire to inflammasomes and induce Alzheimer’s pathology J Cell Mol Med 2008 12 2255 2262 18793350 PMC4514104
- [99]de Vasconcelos NM Van Opdenbosch N Lamkanfi M Inflammasomes as polyvalent cell death platforms Cell Mol Life Sci CMLS 2016 73 2335 2347 27048821 PMC11108487
- [100]Liu L Chan C The role of inflammasome in Alzheimer’s disease Ageing Res Rev 2014 15 6 15 24561250 PMC4029867
- [101]Tan M-S Yu J-T Jiang T Zhu X-C Tan L The NLRP3 inflammasome in Alzheimer’s disease Mol Neurobiol 2013 48 875 882 23686772
- [102]Heneka MT Golenbock DT Latz E Innate immunity in Alzheimer’s disease Nat Immunol 2015 16 229 236 25689443
- [103]Cagnin A Brooks DJ Kennedy AM Gunn RN Myers R Turkheimer FE In-vivo measurement of activated microglia in dementia Lancet Lond Engl 2001 358 461 467 11513911
- [105]Okello A Edison P Archer HA Turkheimer FE Kennedy J Bullock R Microglial activation and amyloid deposition in mild cognitive impairment: a PET study Neurology 2009 72 56 62 19122031 PMC2817573
- [106]Crack PJ Bray PJ Toll-like receptors in the brain and their potential roles in neuropathology Immunol Cell Biol 2007 85 476 480 17667932
- [107]Kawai T Akira S The role of pattern-recognition receptors in innate immunity: update on toll-like receptors Nat Immunol 2010 11 373 384 20404851
- [109]Fassbender K Walter S Kühl S Landmann R Ishii K Bertsch T The LPS receptor (CD14) links innate immunity with Alzheimer’s disease FASEB J Off Publ Fed Am Soc Exp Biol 2004 18 203 205 14597556
- [110]Kielian T Toll-like receptors in central nervous system glial inflammation and homeostasis J Neurosci Res 2006 83 711 730 16541438 PMC2440498
- [111]Scholtzova H Kascsak RJ Bates KA Boutajangout A Kerr DJ Meeker HC Induction of toll-like receptor 9 signaling as a method for ameliorating Alzheimer’s disease-related pathology J Neurosci 2009 29 1846 1854 19211891 PMC2699573
- [112]Liu S Liu Y Hao W Wolf L Kiliaan AJ Penke B TLR2 is a primary receptor for Alzheimer’s amyloid β peptide to trigger neuroinflammatory activation J Immunol 2012 188 1098 1107 22198949
- [113]Perkins ND Integrating cell-signalling pathways with NF-kappaB and IKK function Nat Rev Mol Cell Biol 2007 8 49 62 17183360
- [116]Jaeger PA Pickford F Sun C-H Lucin KM Masliah E Wyss-Coray T Regulation of amyloid precursor protein processing by the Beclin 1 complex PLoS One 2010 5 e11102 20559548 PMC2886067
- [117]Salminen A Kaarniranta K Kauppinen A Ojala J Haapasalo A Soininen H Impaired autophagy and APP processing in Alzheimer’s disease: the potential role of Beclin 1 interactome Prog Neurobiol 2013 106–107 33 54 23827971
- [120]Wang Y Cella M Mallinson K Ulrich JD Young KL Robinette ML TREM2 lipid sensing sustains the microglial response in an Alzheimer’s disease model Cell 2015 160 1061 1071 25728668 PMC4477963
- [122]Pottier C Wallon D Rousseau S Rovelet-Lecrux A Richard A-C Rollin-Sillaire A TREM2 R47H variant as a risk factor for early-onset Alzheimer’s disease J Alzheimers Dis JAD 2013 35 45 49 23380991
- [123]Jonsson T Stefansson H Steinberg S Jonsdottir I Jonsson PV Snaedal J Variant of TREM2 associated with the risk of Alzheimer’s disease N Engl J Med 2013 368 107 116 23150908 PMC3677583
- [124]Lill CM Rengmark A Pihlstrøm L Fogh I Shatunov A Sleiman PM The role of TREM2 R47H as a risk factor for Alzheimer’s disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson’s disease Alzheimers Dement J Alzheimers Assoc 2015 11 1407 1416 PMC4627856 25936935
- [127]Colonna M Wang Y TREM2 variants: new keys to decipher Alzheimer disease pathogenesis Nat Rev Neurosci 2016 17 201 207 26911435
- [131]McNaull BBA Todd S McGuinness B Passmore AP Inflammation and anti-inflammatory strategies for Alzheimer’s disease—a mini-review Gerontology 2010 56 3 14 19752507
- [132]Rubio-Perez JM Morillas-Ruiz JM A review: inflammatory process in Alzheimer’s disease, role of cytokines ScientificWorldJournal 2012 2012 756357 22566778 PMC3330269
- [133]McAfoose J Baune BT Evidence for a cytokine model of cognitive function Neurosci Biobehav Rev 2009 33 355 366 18996146
- [134]Delaby C Gabelle A Blum D Schraen-Maschke S Moulinier A Boulanghien J Central nervous system and peripheral inflammatory processes in Alzheimer’s disease: biomarker profiling approach Front Neurol 2015 6 181 26379616 PMC4547499
- [136]Zambrano A Otth C Mujica L Concha II Maccioni RB Interleukin-3 prevents neuronal death induced by amyloid peptide BMC Neurosci 2007 8 82 17915029 PMC2089076
- [137]Natarajan C Sriram S Muthian G Bright JJ Signaling through JAK2-STAT5 pathway is essential for IL-3-induced activation of microglia Glia 2004 45 188 196 14730712
- [138]Smith JA Das A Ray SK Banik NL Role of pro-inflammatory cytokines released from microglia in neurodegenerative diseases Brain Res Bull 2012 87 10 20 22024597 PMC9827422
- [140]Latta CH Sudduth TL Weekman EM Brothers HM Abner EL Popa GJ Determining the role of IL-4 induced neuroinflammation in microglial activity and amyloid-β using BV2 microglial cells and APP/PS1 transgenic mice J Neuroinflammation 2015 12 41 25885682 PMC4350455
- [141]Liu C Cui G Zhu M Kang X Guo H Neuroinflammation in Alzheimer’s disease: chemokines produced by astrocytes and chemokine receptors Int J Clin Exp Pathol 2014 7 8342 8355 25674199 PMC4314046
- [143]Aloisi F Penna G Cerase J Menéndez Iglesias B Adorini L IL-12 production by central nervous system microglia is inhibited by astrocytes J Immunol Baltim Md 1950 1997 159 1604 1612 9257819
- [144]Vom Berg J Prokop S Miller KR Obst J Kälin RE Lopategui-Cabezas I Inhibition of IL-12/IL-23 signaling reduces Alzheimer’s disease-like pathology and cognitive decline Nat Med 2012 18 1812 1819 23178247
- [145]Bishnoi RJ Palmer RF Royall DR Serum interleukin (IL)-15 as a biomarker of Alzheimer’s disease PLoS One 2015 10 e0117282 25710473 PMC4339977
- [146]Rentzos M Rombos A The role of IL-15 in central nervous system disorders Acta Neurol Scand 2012 125 77 82 21615353
- [147]Sutinen EM Pirttilä T Anderson G Salminen A Ojala JO Pro-inflammatory interleukin-18 increases Alzheimer’s disease-associated amyloid-β production in human neuron-like cells J Neuroinflammation 2012 9 199 22898493 PMC3458954
- [148]Salani F Ciaramella A Bizzoni F Assogna F Caltagirone C Spalletta G Increased expression of interleukin-18 receptor in blood cells of subjects with mild cognitive impairment and Alzheimer’s disease Cytokine 2013 61 360 363 23201485
- [149]Yasuoka S Kawanokuchi J Parajuli B Jin S Doi Y Noda M Production and functions of IL-33 in the central nervous system Brain Res 2011 1385 8 17 21349253
- [151]Zheng C Zhou X-W Wang J-Z The dual roles of cytokines in Alzheimer’s disease: update on interleukins, TNF-α, TGF-β and IFN-γ Transl Neurodegener 2016 5 7 27054030 PMC4822284
- [152]Sriram K O’Callaghan JP Divergent roles for tumor necrosis factor-alpha in the brain J Neuroimmune Pharmacol Off J Soc NeuroImmune Pharmacol 2007 2 140 153 18040839
- [153]Rocha NP Teixeira AL Coelho FM Caramelli P Guimarães HC Barbosa IG Peripheral blood mono-nuclear cells derived from Alzheimer’s disease patients show elevated baseline levels of secreted cytokines but resist stimulation with β-amyloid peptide Mol Cell Neurosci 2012 49 77 84 21971579
- [155]Hsieh H-L Yang C-M Role of redox signaling in neuroinflammation and neurodegenerative diseases Biomed Res Int 2013 2013 484613 24455696 PMC3884773
- [156]Fischer R Maier O Siegemund M Wajant H Scheurich P Pfizenmaier K A TNF receptor 2 selective agonist rescues human neurons from oxidative stress-induced cell death PLoS One 2011 6 e27621 22110694 PMC3215731
- [157]Chiarini A Dal Pra I Whitfield JF Armato U The killing of neurons by beta-amyloid peptides, prions, and pro-inflammatory cytokines Ital J Anat Embryol Arch Ital Anat Ed Embriologia 2006 111 221 246 17385278
- [158]Kempuraj D Khan MM Thangavel R Xiong Z Yang E Zaheer A Glia maturation factor induces interleukin-33 release from astrocytes: implications for neurodegenerative diseases J Neuroimmune Pharmacol Off J Soc NeuroImmune Pharmacol 2013 8 643 650 PMC3660415 23397250
- [159]Ryu JK Cho T Choi HB Jantaratnotai N McLarnon JG Pharmacological antagonism of interleukin-8 receptor CXCR2 inhibits inflammatory reactivity and is neuroprotective in an animal model of Alzheimer’s disease J Neuroinflammation 2015 12 144 26255110 PMC4529987
- [160]Morrison RS Kinoshita Y Johnson MD Guo W Garden GA p53-dependent cell death signaling in neurons Neurochem Res 2003 28 15 27 12587660
- [161]Culmsee C Mattson MP p53 in neuronal apoptosis Biochem Biophys Res Commun 2005 331 761 777 15865932
- [162]Chang JR Ghafouri M Mukerjee R Bagashev A Chabrashvili T Sawaya BE Role of p53 in neurodegenerative diseases Neurodegener Dis 2012 9 68 80 22042001 PMC3304514
- [163]Lanni C Uberti D Racchi M Govoni S Memo M Unfolded p53: a potential biomarker for Alzheimer’s disease J Alzheimers Dis JAD 2007 12 93 99 17851197
- [164]Bartel DP MicroRNAs: genomics, biogenesis, mechanism, and function Cell 2004 116 281 297 14744438
- [166]Eun B Cho B Moon Y Kim SY Kim K Kim H Induction of neuronal apoptosis by expression of Hes6 via p53-dependent pathway Brain Res 2010 1313 1 8 19968968
- [167]Hooper C Meimaridou E Tavassoli M Melino G Lovestone S Killick R p53 is upregulated in Alzheimer’s disease and induces tau phosphorylation in HEK293a cells Neurosci Lett 2007 418 34 37 17399897 PMC1885960
- [168]Maddocks ODK Vousden KH Metabolic regulation by p53 J Mol Med Berl Ger 2011 89 237 245 PMC3043245 21340684
- [169]Vousden KH Alternative fuel—another role for p53 in the regulation of metabolism Proc Natl Acad Sci U S A 2010 107 7117 7118 20393124 PMC2867698
- [171]Buizza L Prandelli C Bonini SA Delbarba A Cenini G Lanni C Conformational altered p53 affects neuronal function: relevance for the response to toxic insult and growth-associated protein 43 expression Cell Death Dis 2013 4 e484 23392172 PMC3734841
- [172]Stanga S Lanni C Govoni S Uberti D D’Orazi G Racchi M Unfolded p53 in the pathogenesis of Alzheimer’s disease: is HIPK2 the link? Aging 2010 2 545 554 20876941 PMC2984604
- [173]Bendotti C Baldessari S Pende M Southgate T Guglielmetti F Samanin R Relationship between GAP-43 expression in the dentate gyrus and synaptic reorganization of hippocampal mossy fibres in rats treated with kainic acid Eur J Neurosci 1997 9 93 101 9042573
- [174]Ambros V Chen X The regulation of genes and genomes by small RNAs Dev Camb Engl 2007 134 1635 1641 17409118
- [175]Leung AKL Sharp PA MicroRNA functions in stress responses Mol Cell 2010 40 205 215 20965416 PMC2996264
- [176]Mendell JT Olson EN MicroRNAs in stress signaling and human disease Cell 2012 148 1172 1187 22424228 PMC3308137
- [177]Holcik M Sonenberg N Translational control in stress and apoptosis Nat Rev Mol Cell Biol 2005 6 318 327 15803138
- [178]Vojta A Zoldoš V Adaptation or malignant transformation: the two faces of epigenetically mediated response to stress Biomed Res Int 2013 2013 954060 24187667 PMC3803131
- [179]Vaseva AV Marchenko ND Ji K Tsirka SE Holzmann S Moll UM p53 opens the mitochondrial permeability transition pore to trigger necrosis Cell 2012 149 1536 1548 22726440 PMC3383624
- [180]Suzuki HI Yamagata K Sugimoto K Iwamoto T Kato S Miyazono K Modulation of microRNA processing by p53 Nature 2009 460 529 533 19626115
- [181]Suzuki HI Miyazono K Dynamics of microRNA biogenesis: crosstalk between p53 network and microRNA processing pathway J Mol Med Berl Ger 2010 88 1085 1094 20614100
Cited by
Sorted by citations
Peripheral cytokine and chemokine alterations in depression: a meta‐analysis of 82 studies
Köhler, C. A., Freitas, T. H., Maes, M., de Andrade, N. Q., Liu, C. S., Fernandes, B. S., Stubbs, B., Solmi, M., Veronese, N., Herrmann, N., et al. (2017) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12698 · Cited by 1,443 · see citing works
Sochocka, M., Donskow-Łysoniewska, K., Diniz, B. S., Kurpas, D., Brzozowska, E., & Leszek, J. (2019) · Molecular Neurobiology · doi:10.1007/s12035-018-1188-4 · Cited by 584 · see citing works
Self-citationImmunosenescence and inflammaging in the aging process: age-related diseases or longevity?
Santoro, A., Bientinesi, E., & Monti, D. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101422 · Cited by 603 · see citing works
Neuroinflammation in frontotemporal dementia
Bright, F., Werry, E. L., Dobson-Stone, C., Piguet, O., Ittner, L. M., Halliday, G. M., Hodges, J. R., Kiernan, M. C., Loy, C. T., Kassiou, M., et al. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0231-z · Cited by 280 · see citing works
Luca, M., Di Mauro, M., Di Mauro, M., & Luca, A. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/4730539 · Cited by 190 · see citing works
Outside in: Unraveling the Role of Neuroinflammation in the Progression of Parkinson's Disease
Troncoso-Escudero, P., Parra, A., Nassif, M., & Vidal, R. L. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00860 · Cited by 191 · see citing works
The mechanism and efficacy of GLP-1 receptor agonists in the treatment of Alzheimer’s disease
Du, H., Meng, X., Yao, Y., & Xu, J. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1033479 · Cited by 125 · see citing works
The molecular pathophysiology of depression and the new therapeutics
Tian, H., Hu, Z., Xu, J., & Wang, C. (2022) · MedComm · doi:10.1002/mco2.156 · Cited by 122 · see citing works
A data-driven approach links microglia to pathology and prognosis in amyotrophic lateral sclerosis
Cooper-Knock, J., Green, C., Altschuler, G., Wei, W., Bury, J. J., Heath, P. R., Wyles, M., Gelsthorpe, C., Highley, J. R., Lorente-Pons, A., et al. (2017) · Acta Neuropathologica Communications · doi:10.1186/s40478-017-0424-x · Cited by 80 · see citing works
HIV TAT-mediated microglial senescence: Role of SIRT3-dependent mitochondrial oxidative stress
Thangaraj, A., Chivero, E. T., Tripathi, A., Singh, S., Niu, F., Guo, M.-L., Pillai, P., Periyasamy, P., & Buch, S. (2021) · Redox Biology · doi:10.1016/j.redox.2020.101843 · Cited by 76 · see citing works
Acoustofluidic assembly of 3D neurospheroids to model Alzheimer's disease
Cai, H., Ao, Z., Hu, L., Moon, Y., Wu, Z., Lu, H.-C., Kim, J., & Guo, F. (2020) · The Analyst · doi:10.1039/d0an01373k · Cited by 70 · see citing works
Tondo, G., Iaccarino, L., Cerami, C., Vanoli, G. E., Presotto, L., Masiello, V., Coliva, A., Salvi, F., Bartolomei, I., Mosca, L., et al. (2020) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.51112 · Cited by 56 · see citing works
Anti-Neuroinflammatory Potential of Polyphenols by Inhibiting NF-Κb to Halt Alzheimer's Disease
Uddin, M. S., Hasana, S., Ahmad, J., Hossain, M. F., Rahman, M. M., Behl, T., Rauf, A., Ahmad, A., Hafeez, A., Perveen, A., et al. (2021) · Current Pharmaceutical Design · doi:10.2174/1381612826666201118092422 · Cited by 49 · see citing works
Cytokine Signalling at the Microglial Penta-Partite Synapse
Aramideh, J. A., Vidal-Itriago, A., Morsch, M., & Graeber, M. B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222413186 · Cited by 35 · see citing works
He, S., Li, X., Mittra, N., Bhattacharjee, A., Wang, H., Song, S., Zhao, S., Liu, F., & Han, X. (2025) · Advanced Science · doi:10.1002/advs.202410910 · Cited by 34 · see citing works
Piovan, A., Battaglia, J., Filippini, R., Dalla Costa, V., Facci, L., Argentini, C., Pagetta, A., Giusti, P., & Zusso, M. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.724993 · Cited by 31 · see citing works
The Role of Complement C3a Receptor in Stroke
Ahmad, S., Bhatia, K., Kindelin, A., & Ducruet, A. F. (2019) · NeuroMolecular Medicine · doi:10.1007/s12017-019-08545-7 · Cited by 21 · see citing works
Immune response of BV-2 microglial cells is impacted by peroxisomal beta-oxidation
Tawbeh, A., Raas, Q., Tahri-Joutey, M., Keime, C., Kaiser, R., Trompier, D., Nasser, B., Bellanger, E., Dessard, M., Hamon, Y., et al. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1299314 · Cited by 18 · see citing works
Wei, J., Liu, C., Qin, D., Ren, F., Duan, J., Chen, T., & Wu, A. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102544 · Cited by 15 · see citing works
- Authors
- Sochocka, M., Diniz, B. S., & Leszek, J.
- Affiliations
- Ludwik Hirszfeld Institute of Immunology and Experimental Therapy (PL)
- The University of Texas Health Science Center at Houston (US)
- Wroclaw Medical University (PL)
- Corresponding author
- Leszek, Jerzy
- Venue
- Molecular Neurobiology
- Published
- 2016-11-26
- Volume
- 54
- Issue
- 10
- Pages
- 8071-8089
- ISSN
- 0893-7648 (ISSN-L)
- 1559-1182
- PMC
- PMC5684251
- OpenAlex
- W2554390311
- Cited by
- 573
- References
- 39
- Citations by year
- 2026: 35 · 2025: 64 · 2024: 64 · 2023: 50 · 2022: 71 · 2021: 111 · 2020: 73 · 2019: 56 · 2018: 31 · 2017: 17
- FWCI
- 3.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Molecular Neurobiology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- 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 › Cancer Research › NF-κB Signaling Pathways
- Keywords
- neuroinflammation, neurodegeneration, microglia, astrocytes, cytokines, Toll-like receptors, p53, NF-κB, neuroprotection, neurogenesis, synaptic plasticity, glial activation
- MeSH terms
- Animals, Astrocytes, Humans, Inflammation, Neurons, NF-kappa B, Microglia, Toll-Like Receptors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review