Role of TGFβ signaling in the pathogenesis of Alzheimer’s disease
Open accessAbstract
Aging is the main risk factor for Alzheimer's disease (AD); being associated with conspicuous changes on microglia activation. Aged microglia exhibit an increased expression of cytokines, exacerbated reactivity to various stimuli, oxidative stress, and reduced phagocytosis of β-amyloid (Aβ). Whereas normal inflammation is protective, it becomes dysregulated in the presence of a persistent stimulus, or in the context of an inflammatory environment, as observed in aging. Thus, neuroinflammation can be a self-perpetuating deleterious response, becoming a source of additional injury to host cells in neurodegenerative diseases. In aged individuals, although transforming growth factor β (TGFβ) is upregulated, its canonical Smad3 signaling is greatly reduced and neuroinflammation persists. This age-related Smad3 impairment reduces protective activation while facilitating cytotoxic activation of microglia through several cellular mechanisms, potentiating microglia-mediated neurodegeneration. Here, we critically discuss the role of TGFβ-Smad signaling on the cytotoxic activation of microglia and its relevance in the pathogenesis of AD. Other protective functions, such as phagocytosis, although observed in aged animals, are not further induced by inflammatory stimuli and TGFβ1. Analysis in silico revealed that increased expression of receptor scavenger receptor (SR)-A, involved in Aβ uptake and cell activation, by microglia exposed to TGFβ, through a Smad3-dependent mechanism could be mediated by transcriptional co-factors Smad2/3 over the MSR1 gene. We discuss that changes of TGFβ-mediated regulation could at least partially mediate age-associated microglia changes, and, together with other changes on inflammatory response, could result in the reduction of protective activation and the potentiation of cytotoxicity of microglia, resulting in the promotion of neurodegenerative diseases.
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IFNγ signaling has been shown to lead to tau phosphorylation and acceleration of neuritic tangle pathology, while TGFβ is a key regulator of various microglial factors including CX3CR1 and numerous interleukins.
“For instance, IFNγ signaling has been shown to lead to tau phosphorylation and acceleration of neuritic tangle pathology while TGFβ has been shown to be a key regulator of various microglial factors including CX3CR1 and numerous interleukins [110, 169].”
From Glial contributions to neurodegeneration in tauopathies (2017) · cites this paper as [169]
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Cites
The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864 · 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
Exploring the full spectrum of macrophage activation
Mosser, D. M., & Edwards, J. P. (2008) · Nature Reviews Immunology · doi:10.1038/nri2448 · Cited by 9,144 · 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
Glutamate neurotoxicity and diseases of the nervous system
Choi, D. W. (1988) · Neuron · doi:10.1016/0896-6273(88)90162-6 · Cited by 8,152 · see citing works
Topological domains in mammalian genomes identified by analysis of chromatin interactions
Dixon, J. R., Selvaraj, S., Yue, F., Kim, A., Li, Y., Shen, Y., Hu, M., Liu, J. S., & Ren, B. (2012) · Nature · doi:10.1038/nature11082 · Cited by 6,829 · see citing works
Alternative activation of macrophages
Gordon, S. (2003) · Nature Reviews Immunology · doi:10.1038/nri978 · Cited by 6,189 · see citing works
Smad-dependent and Smad-independent pathways in TGF-β family signalling
Derynck, R., & Zhang, Y. E. (2003) · Nature · doi:10.1038/nature02006 · Cited by 5,370 · see citing works
Inflamm‐aging: An Evolutionary Perspective on Immunosenescence
FRANCESCHI, C., BONAFÈ, M., VALENSIN, S., OLIVIERI, F., DE LUCA, M., OTTAVIANI, E., & DE BENEDICTIS, G. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06651.x · Cited by 5,358 · see citing works
Inflammation and Alzheimer’s disease
Akiyama, H. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00124-x · Cited by 4,514 · see citing works
Alzheimer's Disease Is a Synaptic Failure
Selkoe, D. J. (2002) · Science · doi:10.1126/science.1074069 · Cited by 4,420 · see citing works
Microglia: a sensor for pathological events in the CNS
Kreutzberg, G. W. (1996) · Trends in Neurosciences · doi:10.1016/0166-2236(96)10049-7 · Cited by 4,396 · 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
Kettenmann, H., Hanisch, U.-K., Noda, M., & Verkhratsky, A. (2011) · Physiological Reviews · doi:10.1152/physrev.00011.2010 · Cited by 3,547 · see citing works
Mechanisms of type-I- and type-II-interferon-mediated signalling
Platanias, L. C. (2005) · Nature reviews. Immunology · doi:10.1038/nri1604 · Cited by 3,480 · see citing works
Macrophage activation and polarization
Martinez, F. O. (2008) · Frontiers in Bioscience · doi:10.2741/2692 · Cited by 3,160 · see citing works
Identification of a unique TGF-β–dependent molecular and functional signature in microglia
Butovsky, O., Jedrychowski, M. P., Moore, C. S., Cialic, R., Lanser, A. J., Gabriely, G., Koeglsperger, T., Dake, B., Wu, P. M., Doykan, C. E., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3599 · Cited by 2,543 · see citing works
Role of Transforming Growth Factor β in Human Disease
Blobe, G. C., Schiemann, W. P., & Lodish, H. F. (2000) · New England Journal of Medicine · doi:10.1056/nejm200005043421807 · Cited by 2,430 · see citing works
Neuroinflammation in Parkinson’s disease: A target for neuroprotection?
Hirsch, E. C., & Hunot, S. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70062-6 · Cited by 1,984 · see citing works
Wen, Z., Zhong, Z., & Darnell, J. E. (1995) · Cell · doi:10.1016/0092-8674(95)90311-9 · Cited by 1,974 · see citing works
The many faces of macrophage activation
Mosser, D. M. (2003) · Journal of Leukocyte Biology · doi:10.1189/jlb.0602325 · Cited by 1,902 · see citing works
Microglial physiology: unique stimuli, specialized responses
Ransohoff, R. M., & Perry, V. H. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132528 · Cited by 1,858 · 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
Microglial Dysfunction and Defective β-Amyloid Clearance Pathways in Aging Alzheimer's Disease Mice
Hickman, S. E., Allison, E. K., & El Khoury, J. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.0616-08.2008 · Cited by 1,329 · cited 3× · see citing works
“…effects depend, at least partly, on the upregulation of Toll-like receptors (TLRs), increased expression of the TLR4 co-receptor CD14 (Letiembre et al., 2007), changes in TLR4 signaling, and changes on the expression profile of scavenger receptors (SRs; Yamamoto et al., 2002; Hickman et al., 2008).”
BackgroundIRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses
Krausgruber, T., Blazek, K. D., Smallie, T., Alzabin, S., Lockstone, H. E., Sahgal, N., Hussell, T., Feldmann, M., & Udalova, I. A. (2011) · Nature Immunology · doi:10.1038/ni.1990 · Cited by 1,296 · see citing works
TGFβ–SMAD signal transduction: molecular specificity and functional flexibility
Schmierer, B., & Hill, C. S. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2297 · Cited by 1,258 · see citing works
Inflammation in Neurodegenerative Disease—A Double-Edged Sword
Wyss-Coray, T., & Mucke, L. (2002) · Neuron · doi:10.1016/s0896-6273(02)00794-8 · Cited by 1,235 · see citing works
Satoh, T., Takeuchi, O., Vandenbon, A., Yasuda, K., Tanaka, Y., Kumagai, Y., Miyake, T., Matsushita, K., Okazaki, T., Saitoh, T., et al. (2010) · Nature Immunology · doi:10.1038/ni.1920 · Cited by 1,156 · see citing works
Debris clearance by microglia: an essential link between degeneration and regeneration
Neumann, H., Kotter, M. R., & Franklin, R. J. M. (2008) · Brain · doi:10.1093/brain/awn109 · Cited by 1,111 · 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
CTCF: an architectural protein bridging genome topology and function
Ong, C., & Corces, V. G. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3663 · Cited by 1,044 · see citing works
Microglia as neuroprotective, immunocompetent cells of the CNS
Streit, W. J. (2002) · Glia · doi:10.1002/glia.10154 · Cited by 919 · see citing works
Inflammatory markers in population studies of aging
Singh, T., & Newman, A. B. (2010) · Ageing Research Reviews · doi:10.1016/j.arr.2010.11.002 · Cited by 866 · see citing works
NF-kB: a crucial transcription factor for glial and neuronal cell function
O'Neill, L. A. J., & Kaltschmidt, C. (1997) · Trends in Neurosciences · doi:10.1016/s0166-2236(96)01035-1 · Cited by 849 · see citing works
Regulation of innate immune responses in the brain
Rivest, S. (2009) · Nature Reviews Immunology · doi:10.1038/nri2565 · Cited by 843 · 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
Godbout, J. P., Chen, J., Abraham, J., Richwine, A. F., Berg, B. M., Kelley, K. W., & Johnson, R. W. (2005) · The FASEB Journal · doi:10.1096/fj.05-3776fje · Cited by 813 · see citing works
Inhibition of transforming growth factor-β/SMAD signalling by the interferon-γ/STAT pathway
Ulloa, L., Doody, J. F., & Massagué, J. (1999) · Nature · doi:10.1038/17826 · Cited by 812 · see citing works
Inflammatory processes in Alzheimer's disease
Heneka, M. T., & O'Banion, M. K. (2007) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2006.11.017 · Cited by 782 · see citing works
Cunningham, C., Wilcockson, D. C., Campion, S., Lunnon, K., & Perry, V. H. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.2614-05.2005 · Cited by 768 · see citing works
Meta-analysis of age-related gene expression profiles identifies common signatures of aging
de Magalhães, J. P., Curado, J., & Church, G. M. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp073 · Cited by 737 · see citing works
Scavenger receptor-mediated adhesion of microglia to β-amyloid fibrils
Khoury, J. E., Hickman, S. E., Thomas, C. A., Cao, L., Silverstein, S. C., & Loike, J. D. (1996) · Nature · doi:10.1038/382716a0 · Cited by 727 · see citing works
Bhat, N. R., Zhang, P., Lee, J. C., & Hogan, E. L. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-05-01633.1998 · Cited by 714 · see citing works
Innate immunity: the missing link in neuroprotection and neurodegeneration?
Nguyen, M. D., Julien, J., & Rivest, S. (2002) · Nature reviews. Neuroscience · doi:10.1038/nrn752 · Cited by 698 · see citing works
Microglia derived from aging mice exhibit an altered inflammatory profile
Sierra, A., Gottfried‐Blackmore, A. C., McEwen, B. S., & Bulloch, K. (2007) · Glia · doi:10.1002/glia.20468 · Cited by 688 · see citing works
MAPK phosphatases — regulating the immune response
Liu, Y., Shepherd, E. G., & Nelin, L. D. (2007) · Nature reviews. Immunology · doi:10.1038/nri2035 · Cited by 679 · see citing works
Microglia in health and disease
Kim, S. U., & de Vellis, J. (2005) · Journal of Neuroscience Research · doi:10.1002/jnr.20562 · Cited by 663 · see citing works
Paresce, D. M., Ghosh, R. N., & Maxfield, F. R. (1996) · Neuron · doi:10.1016/s0896-6273(00)80187-7 · Cited by 663 · see citing works
Porta, C., Rimoldi, M., Raes, G., Brys, L., Ghezzi, P., Di Liberto, D., Dieli, F., Ghisletti, S., Natoli, G., De Baetselier, P., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0809784106 · Cited by 627 · see citing works
New concepts in the immunopathogenesis of multiple sclerosis
Hemmer, B., Archelos, J., & Hartung, H. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn784 · Cited by 605 · see citing works
TGF-β1 promotes microglial amyloid-β clearance and reduces plaque burden in transgenic mice
Wyss-Coray, T., Lin, C., Yan, F., Yu, G.-Q., Rohde, M., McConlogue, L., Masliah, E., & Mucke, L. (2001) · Nature Medicine · doi:10.1038/87945 · Cited by 587 · see citing works
Master Transcription Factors Determine Cell-Type-Specific Responses to TGF-β Signaling
Mullen, A. C., Orlando, D. A., Newman, J. J., Lovén, J., Kumar, R., Bilodeau, S., Reddy, J., Guenther, M. G., DeKoter, R. P., & Young, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.08.050 · Cited by 563 · see citing works
The TGFbeta Superfamily Signaling Pathway
Weiss, A., & Attisano, L. (2012) · Wiley Interdisciplinary Reviews Developmental Biology · doi:10.1002/wdev.86 · Cited by 563 · see citing works
Microglial cell dysregulation in brain aging and neurodegeneration
von Bernhardi, R., Eugenín-von Bernhardi, L., & Eugenín, J. (2015) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00124 · Cited by 556 · see citing works
Self-citationBoutros, T., Chevet, É., & Metrakos, P. P. (2008) · Pharmacological Reviews · doi:10.1124/pr.107.00106 · Cited by 545 · see citing works
Aging as an event of proteostasis collapse
Taylor, R. C., & Dillin, A. (2011) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a004440 · Cited by 538 · 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
Diabetes and the Brain: Oxidative Stress, Inflammation, and Autophagy
Muriach, M., Flores‐Bellver, M., Romero, F. J., & Barcia, J. M. (2014) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2014/102158 · Cited by 488 · see citing works
Glucocorticoids inhibit MAP kinase via increased expression and decreased degradation of MKP‐1
Kassel, O., Sancono, A., Krätzschmar, J., Kreft, B., Stassen, M., & Cato, A. C. B. (2001) · The EMBO Journal · doi:10.1093/emboj/20.24.7108 · Cited by 478 · see citing works
Age-Specific Epigenetic Drift in Late-Onset Alzheimer's Disease
Wang, S.-C., Oelze, B., & Schumacher, A. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002698 · Cited by 467 · see citing works
Motif module map reveals enforcement of aging by continual NF-κB activity
Adler, A. S., Sinha, S., Kawahara, T. L. A., Zhang, J. Y., Segal, E., & Chang, H. Y. (2007) · Genes & Development · doi:10.1101/gad.1588507 · Cited by 466 · see citing works
The microglial "activation" continuum: from innate to adaptive responses
Town, T., Nikolic, V., & Tan, J. (2005) · Journal of Neuroinflammation · doi:10.1186/1742-2094-2-24 · Cited by 456 · see citing works
Eljaschewitsch, E., Witting, A., Mawrin, C., Lee, T., Schmidt, P. M., Wolf, S., Hoertnagl, H., Raine, C. S., Schneider-Stock, R., Nitsch, R., et al. (2006) · Neuron · doi:10.1016/j.neuron.2005.11.027 · Cited by 445 · see citing works
Neuroinflammatory processes in Alzheimer’s disease
Heneka, M. T., O’Banion, M. K., Terwel, D., & Kummer, M. P. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0438-z · Cited by 433 · see citing works
Redox regulation of glial inflammatory response to lipopolysaccharide and interferonγ
Pawate, S., Shen, Q., Fan, F., & Bhat, N. R. (2004) · Journal of Neuroscience Research · doi:10.1002/jnr.20180 · Cited by 428 · see citing works
Blocking TGF-β–Smad2/3 innate immune signaling mitigates Alzheimer-like pathology
Town, T., Laouar, Y., Pittenger, C., Mori, T., Szekely, C. A., Tan, J., Duman, R. S., & Flavell, R. A. (2008) · Nature Medicine · doi:10.1038/nm1781 · Cited by 422 · see citing works
Amyloidogenic role of cytokine TGF-β1 in transgenic mice and in Alzheimer's disease
Wyss-Coray, T., Masliah, E., Mallory, M., McConlogue, L., Johnson-Wood, K., Lin, C., & Mucke, L. (1997) · Nature · doi:10.1038/39321 · Cited by 417 · see citing works
He, P., Zhong, Z., Lindholm, K., Berning, L., Lee, W., Lemere, C., Staufenbiel, M., Li, R., & Shen, Y. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200705042 · Cited by 390 · see citing works
Reimagining Alzheimer's Disease—An Age-Based Hypothesis
Herrup, K. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.4521-10.2010 · Cited by 386 · see citing works
How the Smads regulate transcription
Ross, S., & Hill, C. S. (2007) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2007.09.006 · Cited by 385 · see citing works
Microglia and inflammatory mechanisms in the clearance of amyloid β peptide
Rogers, J., Strohmeyer, R., Kovelowski, C. J., & Li, R. (2002) · Glia · doi:10.1002/glia.10153 · Cited by 381 · see citing works
Gabuzda, D., Busciglio, J., Chen, L. B., Matsudaira, P., & Yankner, B. A. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)36875-8 · Cited by 373 · see citing works
TGF‐β signaling: A tale of two responses
Rahimi, R. A., & Leof, E. B. (2007) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21501 · Cited by 371 · see citing works
Targeting p38 MAPK pathway for the treatment of Alzheimer's disease
Munoz, L., & Ammit, A. J. (2009) · Neuropharmacology · doi:10.1016/j.neuropharm.2009.11.010 · Cited by 370 · see citing works
Phospho-control of TGF-β superfamily signaling
Wrighton, K. H., Lin, X., & Feng, X. (2008) · Cell Research · doi:10.1038/cr.2008.327 · Cited by 366 · see citing works
Tarkowski, E., Issa, R., Sjögren, M., Wallin, A., Blennow, K., Tarkowski, A., & Kumar, P. (2002) · Neurobiology of Aging · doi:10.1016/s0197-4580(01)00285-8 · Cited by 360 · see citing works
Akama, K. T., & Eldik, L. J. V. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.11.7918 · Cited by 356 · see citing works
Deficiency in neuronal TGF-β signaling promotes neurodegeneration and Alzheimer’s pathology
Tesseur, I., Zou, K., Esposito, L., Bard, F., Berber, E., Can, J. V., Lin, A. H., Crews, L., Tremblay, P., Mathews, P., et al. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27341 · Cited by 355 · see citing works
Akama, K. T., Albanese, C., Pestell, R. G., & Eldik, L. J. V. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.10.5795 · Cited by 348 · see citing works
Role of Smads in TGFβ signaling
Heldin, C., & Moustakas, A. (2011) · Cell and Tissue Research · doi:10.1007/s00441-011-1190-x · Cited by 335 · 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
Aging of the Immune System as a Prognostic Factor for Human Longevity
Larbi, A., Franceschi, C., Mazzatti, D. J., Solana, R., Wikby, A., & Pawelec, G. (2008) · Physiology · doi:10.1152/physiol.00040.2007 · Cited by 316 · see citing works
Dean, J. L. E., Sully, G., Clark, A. R., & Saklatvala, J. (2004) · Cellular Signalling · doi:10.1016/j.cellsig.2004.04.006 · Cited by 308 · see citing works
Medeiros, R., Prediger, R. D. S., Passos, G. F., Pandolfo, P., Duarte, F. S., Franco, J. L., Dafre, A. L., Di Giunta, G., Figueiredo, C. P., Takahashi, R. N., et al. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.5047-06.2007 · Cited by 292 · see citing works
IFNγ signaling—Does it mean JAK–STAT?
Gough, D. J., Levy, D. E., Johnstone, R. W., & Clarke, C. J. (2008) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2008.08.004 · Cited by 290 · see citing works
Saha, R. N., Jana, M., & Pahan, K. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.10.7101 · Cited by 290 · see citing works
Molecular consequences of activated microglia in the brain: overactivation induces apoptosis
Liu, B., Wang, K., Gao, H.-M., Mandavilli, B., Wang, J.-Y., & Hong, J.-S. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.t01-1-00216.x · Cited by 286 · see citing works
Chu, C. T., Levinthal, D. J., Kulich, S. M., Chalovich, E. M., & DeFranco, D. B. (2004) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.2004.04132.x · Cited by 273 · see citing works
Slow Degradation of Aggregates of the Alzheimer's Disease Amyloid β-Protein by Microglial Cells
Paresce, D. M., Chung, H., & Maxfield, F. R. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.46.29390 · Cited by 269 · see citing works
Astrocytes Regulate Microglial Phagocytosis of Senile Plaque Cores of Alzheimer's Disease
DeWitt, D. A., Perry, G., Cohen, M., Doller, C., & Silver, J. (1998) · Experimental Neurology · doi:10.1006/exnr.1997.6738 · Cited by 261 · cited 1× · see citing works
“Microglial cell reactivity to Aβ and phagocytic activity are modulated by astrocytes, attenuating the cytotoxic response of microglia (DeWitt et al., 1998; von Bernhardi and Ramírez, 2001).”
BackgroundNeuronal changes in normal human aging and Alzheimer's disease.
Uylings, H., & de Brabander, J. D. (2002) · Brain and Cognition · doi:10.1006/brcg.2001.1500 · Cited by 260 · see citing works
Aging‐dependent changes of microglial cells and their relevance for neurodegenerative disorders
Von Bernhardi, R., Tichauer, J. E., & Eugenín, J. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06537.x · Cited by 258 · see citing works
Self-citationThe Essential Involvement of Cross-Talk between IFN-γ and TGF-β in the Skin Wound-Healing Process
Ishida, Y., Kondo, T., Takayasu, T., Iwakura, Y., & Mukaida, N. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.3.1848 · Cited by 257 · see citing works
Doyle, K. P., Cekanaviciute, E., Mamer, L., & Buckwalter, M. S. (2010) · Journal of Neuroinflammation · doi:10.1186/1742-2094-7-62 · Cited by 250 · see citing works
Regulating Factors for Microglial Activation.
Nakamura, Y. (2002) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.25.945 · Cited by 241 · see citing works
Calabrese, V., Guagliano, E., Sapienza, M. A., Panebianco, M., Calafato, S., Puleo, E., Pennisi, G., Mancuso, C., Butterfield, D. A., & Stella, A. G. (2006) · Neurochemical Research · doi:10.1007/s11064-006-9203-y · Cited by 241 · see citing works
Inflammatory Aspects of Alzheimer Disease and Other Neurodegenerative Disorders
Schwab, C., & McGeer, P. L. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-13402 · Cited by 234 · see citing works
Helenius, M., Hänninen, M., Lehtinen, S. K., & Salminen, A. (1996) · Biochemical Journal · doi:10.1042/bj3180603 · Cited by 232 · see citing works
Peripheral infection evokes exaggerated sickness behaviour in pre-clinical murine prion disease
Combrinck, M. I., Perry, V. H., & Cunningham, C. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00030-1 · Cited by 231 · see citing works
CTCF: the protein, the binding partners, the binding sites and their chromatin loops
Holwerda, S. J. B., & de Laat, W. L. (2013) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2012.0369 · Cited by 230 · see citing works
Transforming Growth Factor-β1 Increases Bad Phosphorylation and Protects Neurons Against Damage
Zhu, Y., Yang, G., Ahlemeyer, B., Pang, L., Che, X., Culmsee, C., Klumpp, S., & Krieglstein, J. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-10-03898.2002 · Cited by 225 · see citing works
Wyss‐Coray, T., Lin, C., Sanan, D. A., Mucke, L., & Masliah, E. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64713-x · Cited by 224 · see citing works
Munoz, L., Ranaivo, H. R., Roy, S. M., Hu, W., Craft, J. M., McNamara, L. K., Chico, L. W., Van Eldik, L. J., & Watterson, D. M. (2007) · Journal of Neuroinflammation · doi:10.1186/1742-2094-4-21 · Cited by 224 · see citing works
Protracted downregulation of CX3CR1 on microglia of aged mice after lipopolysaccharide challenge
Wynne, A. M., Henry, C. J., Huang, Y., Cleland, A., & Godbout, J. P. (2010) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.05.011 · Cited by 224 · see citing works
P38 MAP kinase is activated at early stages in Alzheimer's disease brain
Sun, A. (2003) · Experimental Neurology · doi:10.1016/s0014-4886(03)00180-8 · Cited by 219 · see citing works
Role of reactive oxygen species in LPS‐induced production of prostaglandin E2in microglia
Wang, T., Qin, L., Liu, B., Liu, Y., Wilson, B. C., Eling, T. E., Langenbach, R. I., Taniura, S., & Hong, J. (2004) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.02242.x · Cited by 218 · see citing works
Frenkel, D., Wilkinson, K., Zhao, L., Hickman, S. E., Means, T. K., Puckett, L., Farfara, D., Kingery, N. D., Weiner, H. L., & El Khoury, J. (2013) · Nature Communications · doi:10.1038/ncomms3030 · Cited by 214 · see citing works
Filippo, M. D., Sarchielli, P., Picconi, B., & Calabresi, P. (2008) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2008.06.005 · Cited by 211 · see citing works
Qin, L., Li, G., Qian, X., Liu, Y., Wu, X., Liu, B., Hong, J., & Block, M. L. (2005) · Glia · doi:10.1002/glia.20225 · Cited by 210 · see citing works
Exploring long-range genome interactions using the WashU Epigenome Browser
Zhou, X., Lowdon, R. F., Li, D., Lawson, H. A., Madden, P. A. F., Costello, J., & Wang, T. (2013) · Nature Methods · doi:10.1038/nmeth.2440 · Cited by 209 · see citing works
Aβ-Induced Inflammatory Processes in Microglia Cells of APP23 Transgenic Mice
Bornemann, K. D., Wiederhold, K., Pauli, C., Ermini, F., Stalder, M., Schnell, L., Sommer, B., Jucker, M., & Staufenbiel, M. (2001) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63945-4 · Cited by 204 · see citing works
Lucas, M., Zhang, X., Prasanna, V., & Mosser, D. M. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.1.469 · Cited by 197 · see citing works
Cytokine Gene Expression as a Function of the Clinical Progression of Alzheimer Disease Dementia
Luterman, J. D., Haroutunian, V., Yemul, S., Ho, L., Purohit, D., Aisen, P. S., Mohs, R., & Pasinetti, G. M. (2000) · Archives of Neurology · doi:10.1001/archneur.57.8.1153 · Cited by 192 · see citing works
Immunological aspects of microglia: relevance to Alzheimer's disease
Benveniste, E. N., Nguyen, V. T., & O'Keefe, G. M. (2001) · Neurochemistry International · doi:10.1016/s0197-0186(01)00045-6 · Cited by 188 · see citing works
Transforming Growth Factor-β1 Inhibition of Macrophage Activation Is Mediated via Smad3
Werner, F., Jain, M. K., Feinberg, M. W., Sibinga, N. E. S., Pellacani, A. U. E., Wiesel, P., Chin, M. T., Topper, J. N., Perrella, M. A., & Lee, M.-E. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m004536200 · Cited by 180 · see citing works
Hayashi, Y., Yoshida, M., Yamato, M., Ide, T., Wu, Z., Ochi-Shindou, M., Kanki, T., Kang, D., Sunagawa, K., Tsutsui, H., et al. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1957-08.2008 · Cited by 180 · see citing works
Li, R., Yang, L., Lindholm, K., Konishi, Y., Yue, X., Hampel, H., Zhang, D., & Shen, Y. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.4580-03.2004 · Cited by 177 · see citing works
Innate immune receptor expression in normal brain aging
Letiembre, M., Hao, W., Liu, Y., Walter, S., Mihaljevic, I., Rivest, S., Hartmann, T., & Fassbender, K. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.01.004 · Cited by 175 · see citing works
Microglia Activation and Anti-inflammatory Regulation in Alzheimer’s Disease
Lue, L., Kuo, Y., Beach, T. G., & Walker, D. G. (2010) · Molecular Neurobiology · doi:10.1007/s12035-010-8106-8 · Cited by 175 · see citing works
Lukiw, W. J. (2004) · Neurochemical Research · doi:10.1023/b:nere.0000023615.89699.63 · Cited by 172 · see citing works
Welser-Alves, J. V., & Milner, R. (2013) · Neurochemistry International · doi:10.1016/j.neuint.2013.04.007 · Cited by 169 · see citing works
Pei, J.-J., Braak, E., Braak, H., Grundke-Iqbal, I., Iqbal, K., Winblad, B., & Cowburn, R. F. (2001) · Journal of Alzheimer's Disease · doi:10.3233/jad-2001-3107 · Cited by 165 · see citing works
Alzheimer's disease β‐secretase BACE1 is not a neuron‐specific enzyme
Roßner, S., Lange‐Dohna, C., Zeitschel, U., & Perez-Polo, J. R. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02857.x · Cited by 161 · see citing works
Prehn, J. H. M., Bindokas, V. P., Jordán, J., Galindo, M. F., Ghadge, G. D., Roos, R. P., Boise, L., Thompson, C. B., Krajewski, S., Reed, J. C., et al. (1996) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)08714-0 · Cited by 161 · see citing works
Microglia Demonstrate Age-Dependent Interaction with Amyloid-β Fibrils
Floden, A. M., & Combs, C. K. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-101014 · Cited by 160 · see citing works
Expression of Scavenger Receptors in Glial Cells
Alarcón, R., Fuenzalida, C., Santibáñez, M., & Rommy von Bernhardi, M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m414686200 · Cited by 158 · see citing works
Delayed Changes in Growth Factor Gene Expression during Slow Remyelination in the CNS of Aged Rats
Hinks, G. L., & Franklin, R. J. M. (2000) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.2000.0897 · Cited by 156 · see citing works
Redox regulation of neuronal survival mediated by electrophilic compounds
Satoh, T., & Lipton, S. A. (2006) · Trends in Neurosciences · doi:10.1016/j.tins.2006.11.004 · Cited by 154 · see citing works
Christie, R. H., Freeman, M. W., & Hyman, B. T. (1996) · PubMed · Cited by 152 · see citing works
Zhu, Y., Culmsee, C., Klumpp, S., & Krieglstein, J. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2003.10.037 · Cited by 149 · see citing works
NF‐κB pathway: a target for preventing β‐amyloid (Aβ)‐induced neuronal damage and Aβ42 production
Valerio, A., Boroni, F., Benarese, M., Sarnico, I., Ghisi, V., Bresciani, L. G., Ferrario, M., Borsani, G., Spano, P., & Pizzi, M. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.04722.x · Cited by 148 · see citing works
Signalling events involved in interferon‐γ‐inducible macrophage nitric oxide generation
Blanchette, J., Jaramillo, M., & Olivier, M. (2003) · Immunology · doi:10.1046/j.1365-2567.2003.01620.x · Cited by 145 · see citing works
Priming of microglia in a DNA-repair deficient model of accelerated aging
Raj, D. D. A., Jaarsma, D., Holtman, I. R., Olah, M., Ferreira, F. M., Schaafsma, W., Brouwer, N., Meijer, M., de Waard, M. C., van der Pluijm, I., et al. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.03.025 · Cited by 144 · see citing works
Tau Therapeutic Strategies for the Treatment of Alzheimers Disease
Churcher, I. (2006) · Current Topics in Medicinal Chemistry · doi:10.2174/156802606776743057 · Cited by 142 · see citing works
Yan, J., Zhang, H., Yin, Y. I., Li, J., Tang, Y., Purkayastha, S., Li, L., & Cai, D. (2014) · Nature Medicine · doi:10.1038/nm.3616 · Cited by 142 · see citing works
Transforming Growth Factor-β1 Potentiates Amyloid-β Generation in Astrocytes and in Transgenic Mice
Lesné, S., Docagne, F., Gabriel, C., Liot, G., Lahiri, D. K., Buée, L., Plawinski, L., Delacourte, A., MacKenzie, E. T., Buisson, A., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300819200 · Cited by 142 · see citing works
Eldik, L. J. V., Thompson, W. L., Ranaivo, H. R., Behanna, H. A., & Watterson, D. M. (2007) · International review of neurobiology · doi:10.1016/s0074-7742(07)82015-0 · Cited by 141 · see citing works
Chromatin and transcriptional signatures for Nodal signaling during endoderm formation in hESCs
Kim, S. W., Yoon, S., Chuong, E. B., Oyolu, C., Wills, A. E., Gupta, R., & Baker, J. C. (2011) · Developmental Biology · doi:10.1016/j.ydbio.2011.06.009 · Cited by 140 · see citing works
Glial cell dysregulation: a new perspective on Alzheimer disease
Rommy von Bernhardi, M. (2007) · Neurotoxicity Research · doi:10.1007/bf03033906 · Cited by 138 · see citing works
TGF-β1 Pathway as a New Target for Neuroprotection in Alzheimer's Disease
Caraci, F., Battaglia, G., Bruno, V., Bosco, P., Carbonaro, V., Giuffrida, M. L., Drago, F., Sortino, M. A., Nicoletti, F., & Copani, A. (2009) · CNS Neuroscience & Therapeutics · doi:10.1111/j.1755-5949.2009.00115.x · Cited by 135 · see citing works
Pineda, J. R., Daynac, M., Chicheportiche, A., Cebrián‐Silla, A., Sii-Felice, K., García‐Verdugo, J. M., Boussin, F. D., & Mouthon, M. (2013) · EMBO Molecular Medicine · doi:10.1002/emmm.201202197 · Cited by 134 · see citing works
β‐amyloid inhibition of long‐term potentiation is mediated via tumor necrosis factor
Wang, Q., Wu, J., Rowan, M. J., & Anwyl, R. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04457.x · Cited by 133 · see citing works
Feijoo, C., Campbell, D. G., Jakes, R., Goedert, M., & Cuenda, A. (2005) · Journal of Cell Science · doi:10.1242/jcs.01655 · Cited by 133 · see citing works
Liu, X., Wu, Z., Hayashi, Y., & Nakanishi, H. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.04.050 · Cited by 132 · see citing works
Kandasamy, M., Lehner, B., Kraus, S., Paul Ramm, S., Marschallinger, J., Rivera, F. J., Trümbach, D., Ueberham, U., Reitsamer, H. A., Strauß, O., et al. (2014) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12298 · Cited by 130 · see citing works
Inhibition of NF-κB-dependent Transcription by MKP-1
King, E. M., Holden, N. S., Gong, W., Rider, C. F., & Newton, R. C. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.028381 · Cited by 129 · see citing works
The DNA Binding Activities of Smad2 and Smad3 Are Regulated by Coactivator-mediated Acetylation
Simonsson, M., Kanduri, M., Gronroos, E. C., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m607868200 · Cited by 129 · see citing works
Dang, P. M., Morel, F., Gougerot‐Pocidalo, M., & Benna, J. E. (2003) · Biochemistry · doi:10.1021/bi0205754 · Cited by 128 · see citing works
Dell'Albani, P., Santangelo, R., Torrisi, L., Nicoletti, V., de Vellis, J., & Stella, A. G. (2001) · Journal of Neuroscience Research · doi:10.1002/jnr.1169 · Cited by 127 · see citing works
Mechanism mediating oligomeric Aβ clearance by naïve primary microglia
Yang, C.-N., Shiao, Y.-J., Shie, F., Guo, B.-S., Chen, P.-H., Cho, C.-Y., Chen, Y., Huang, F.-L., & Tsay, H.-J. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.01.005 · Cited by 125 · see citing works
Alzheimer 100 – highlights in the history of Alzheimer research
Jellinger, K. A. (2006) · Journal of Neural Transmission · doi:10.1007/s00702-006-0578-3 · Cited by 124 · see citing works
Handattu, S. P., Garber, D. W., Monroe, C. E., van Groen, T., Kadish, I., Nayyar, G., Cao, D., Palgunachari, M. N., Li, L., & Anantharamaiah, G. M. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.03.007 · Cited by 124 · see citing works
Abutbul, S., Shapiro, J., Szaingurten‐Solodkin, I., Levy, N., Carmy, Y., Baron, R., Jung, S., & Monsonego, A. (2012) · Glia · doi:10.1002/glia.22343 · Cited by 122 · see citing works
Marcus, J. S., Karackattu, S. L., Fleegal, M. A., & Sumners, C. (2002) · Glia · doi:10.1002/glia.10168 · Cited by 120 · see citing works
Transforming growth factor-beta 1 inhibits scavenger receptor activity in THP-1 human macrophages.
Bottalico, L. A., Wager, R. E., Agellon, L. B., Assoian, R. K., & Tabas, I. A. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)54434-3 · Cited by 114 · see citing works
Transforming Growth Factor-β: A Neuroprotective Factor in Cerebral Ischemia
Dhandapani, K. M., & Brann, D. W. (2003) · Cell Biochemistry and Biophysics · doi:10.1385/cbb:39:1:13 · Cited by 111 · see citing works
Li, L., Lu, J., Tay, S. S. W., Moochhala, S., & He, B. P. (2007) · Brain Research · doi:10.1016/j.brainres.2007.04.066 · Cited by 110 · see citing works
Genomic structure, induction, and production of TNF-alpha.
Spriggs, D. R., Deutsch, S., & Kufe, D. W. (1992) · PubMed · Cited by 107 · see citing works
TGF-β1 downregulates CD36 and scavenger receptor A but upregulates LOX-1 in human macrophages
Draude, G., & Lorenz, R. L. (2000) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.2000.278.4.h1042 · Cited by 105 · see citing works
Reversal of aging by NFκB blockade
Adler, A. S., Kawahara, T. L. A., Segal, E., & Chang, H. Y. (2008) · Cell Cycle · doi:10.4161/cc.7.5.5490 · Cited by 99 · see citing works
Tgfβ signaling regulates temporal neurogenesis and potency of neural stem cells in the CNS
Dias, J. M., Alekseenko, Z., Applequist, J. M., & Ericson, J. (2014) · Neuron · doi:10.1016/j.neuron.2014.10.033 · Cited by 99 · see citing works
Lee, S. Y., Lee, J. W., Lee, H., Yoo, H. S., Yun, Y. P., Oh, K. W., Ha, T. Y., & Hong, J. T. (2005) · Molecular Brain Research · doi:10.1016/j.molbrainres.2005.07.009 · Cited by 98 · see citing works
Age-dependent changes on TGFβ1 Smad3 pathway modify the pattern of microglial cell activation
Tichauer, J. E., Flores, B., Soler, B., Bernhardi, L. E.-V., Ramírez, G., & Rommy von Bernhardi, M. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2013.12.018 · Cited by 97 · see citing works
Microglial reactivity to β-amyloid is modulated by astrocytes and proinflammatory factors
Rommy von Bernhardi, M., & Eugenín, J. L. (2004) · Brain Research · doi:10.1016/j.brainres.2004.07.084 · Cited by 97 · see citing works
Self-citationNeuro–glia interaction effects on GFAP gene: a novel role for transforming growth factor‐β1
Spohr, T. C. L. D. S. E., Martinez, R., Silva, E. F. D., Moura‐Neto, V., & Gomes, F. C. A. (2002) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2002.02283.x · Cited by 97 · see citing works
TGF-β1 upregulates CX3CR1 expression and inhibits fractalkine-stimulated signaling in rat microglia
Chen, S., Luo, D., Streit, W. J., & Harrison, J. K. (2002) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(02)00354-5 · Cited by 96 · see citing works
Tran, M. H., Yamada, K., Olariu, A., Mizuno, M., Ren, X. H., & Nabeshima, T. (2001) · The FASEB Journal · doi:10.1096/fj.00-0719fje · Cited by 95 · see citing works
Tu, A. W., & Luo, K. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700085200 · Cited by 93 · see citing works
Altered subcellular location of phosphorylated Smads in Alzheimer's disease
Ueberham, U., Ueberham, E., Gruschka, H., & Arendt, T. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.05109.x · Cited by 93 · 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
Jono, H., Xu, H., Kai, H., LIM, D. J., Kim, Y. S., Feng, X., & Li, J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301773200 · Cited by 87 · see citing works
Imoto, S., Sugiyama, K., Muromoto, R., Sato, N., Yamamoto, T., & Matsuda, T. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304961200 · Cited by 85 · see citing works
Nakajima, K., Tohyama, Y., Maeda, S., Kohsaka, S., & Kurihara, T. (2007) · Neurochemistry International · doi:10.1016/j.neuint.2007.02.006 · Cited by 81 · see citing works
Venema, R. C., Venema, V. J., Eaton, D. C., & Marrero, M. B. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.46.30795 · Cited by 81 · see citing works
Argmann, C., Diepstraten, C. V. D., Sawyez, C. G., Edwards, J. Y., Hegele, R. A., Wolfe, B. M. J., & Huff, M. W. (2001) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/hq1201.099426 · Cited by 81 · see citing works
Inhibition of LPS-induced iNOS and NO synthesis in primary rat microglial cells
Lieb, K. (2002) · Neurochemistry International · doi:10.1016/s0197-0186(02)00076-1 · Cited by 80 · see citing works
Mocali, A., Cedrola, S., Malva, N. D., Bontempelli, M., Costanza, V. A. M., Bavazzano, A., Comolli, R., Paoletti, F., & Porta, C. A. M. L. (2004) · Experimental Gerontology · doi:10.1016/j.exger.2004.07.007 · Cited by 79 · see citing works
Microglia astrocyte interaction in Alzheimer's disease: friends or foes for the nervous system?
Rommy von Bernhardi, M., & Ramírez, G. (2001) · Biological Research · doi:10.4067/s0716-97602001000200017 · Cited by 79 · see citing works
TGF-β1 protects against Aβ-neurotoxicity via the phosphatidylinositol-3-kinase pathway
Caraci, F., Battaglia, G., Busceti, C., Biagioni, F., Mastroiacovo, F., Bosco, P., Drago, F., Nicoletti, F., Sortino, M. A., & Copani, A. (2008) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.01.007 · Cited by 79 · see citing works
Transforming Growth Factor 1 Modulates Cell Migration in Rat Cortex: Effects of Ethanol
Siegenthaler, J. A. (2004) · Cerebral Cortex · doi:10.1093/cercor/bhh039 · Cited by 78 · see citing works
Docagne, F., Nicole, O., Gabriel, C., Fernández‐Monreal, M., Lesné, S., Ali, C., Plawinski, L., Carmeliet, P., MacKenzie, E. T., Buisson, A., et al. (2002) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.2002.1206 · Cited by 77 · see citing works
Aging Accelerates Endotoxin-Induced Thrombosis
Yamamoto, K., Shimokawa, T., Yi, H., Isobe, K., Kojima, T., Loskutoff, D. J., & Saito, H. (2002) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64457-4 · Cited by 76 · see citing works
Inhibition of Aβ production by NF-κB inhibitors
Paris, D., Patel, N., Quadros, A., Linan, M., Bakshi, P., Ait-Ghezala, G., & Mullan, M. (2007) · Neuroscience Letters · doi:10.1016/j.neulet.2006.12.029 · Cited by 75 · see citing works
Cytokine modulation of murine microglial cell superoxide production
Hu, S., Sheng, W. S., Peterson, P. K., et al. (1995) · Glia · doi:10.1002/glia.440130106 · Cited by 75 · see citing works
Herrera‐Molina, R., & Rommy von Bernhardi, M. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.01.003 · Cited by 74 · see citing works
Lee, H., Ueda, M., Zhu, X., Perry, G. L., & Smith, M. A. (2006) · Journal of Neuroscience Research · doi:10.1002/jnr.21072 · Cited by 72 · see citing works
Smad3 phosphorylation by cyclin-dependent kinases
LIU, F. (2006) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2005.09.010 · Cited by 71 · see citing works
Amara, F., Junaid, A., Clough, R. R., & Liang, B. (1999) · Molecular Brain Research · doi:10.1016/s0169-328x(99)00158-8 · Cited by 70 · see citing works
Tichauer, J. E., Saud, K., & Rommy von Bernhardi, M. (2007) · NeuroImmunoModulation · doi:10.1159/000110642 · Cited by 68 · see citing works
An integrative ChIP-chip and gene expression profiling to model SMAD regulatory modules
Qin, H., Chan, M. W., Liyanarachchi, S., Balch, C., Potter, D., Souriraj, I. J., Cheng, A. S. L., Agosto-Perez, F., Nikonova, E. V., Yan, P. S., et al. (2009) · BMC Systems Biology · doi:10.1186/1752-0509-3-73 · Cited by 67 · see citing works
A Role for TGF-β Signaling in Neurodegeneration: Evidence from Genetically Engineered Models
Tesseur, I. C., & Wyss‐Coray, T. (2006) · Current Alzheimer Research · doi:10.2174/156720506779025297 · Cited by 66 · see citing works
Burton, T. R., Liang, B., Dibrov, A., & Amara, F. (2002) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)00725-8 · Cited by 64 · see citing works
Functional Aspects of Redox Control During Neuroinflammation
Rosales‐Corral, S., Reiter, R. J., Tan, D., Ortiz, G. G., & López-Armas, G. D. C. (2009) · Antioxidants and Redox Signaling · doi:10.1089/ars.2009.2629 · Cited by 64 · see citing works
Jang, B., Lim, K.-J., Suh, M., Park, J.-G., & Suh, S. (2007) · FEMS Immunology & Medical Microbiology · doi:10.1111/j.1574-695x.2007.00293.x · Cited by 63 · see citing works
Ramírez, G., Toro, R., Döbeli, H., & von Bernhardi, R. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.01.007 · Cited by 60 · see citing works
Self-citationTGF-β1 Disrupts Endotoxin Signaling in Microglial Cells through Smad3 and MAPK Pathways
Le, Y., Iribarren, P., Gong, W., Cui, Y., Zhang, X., & Wang, J. M. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.2.962 · Cited by 58 · see citing works
Katsel, P., Davis, K. L., & Haroutunian, V. H. (2005) · International review of neurobiology · doi:10.1016/s0074-7742(05)63003-6 · Cited by 56 · see citing works
Johns, L. D., Babcock, G., Green, D., Freedman, M. S., Sriram, S., & Ransohoff, R. M. (1992) · Brain Research · doi:10.1016/0006-8993(92)91211-v · Cited by 56 · see citing works
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The Amyloid-β Pathway in Alzheimer’s Disease
Hampel, H., Hardy, J., Blennow, K., Chen, C., Perry, G., Kim, S. H., Villemagne, V. L., Aisen, P., Vendruscolo, M., Iwatsubo, T., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01249-0 · Cited by 1,952 · see citing works
Glial contributions to neurodegeneration in tauopathies
Leyns, C. E. G., & Holtzman, D. M. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0192-x · Cited by 409 · see citing works
Time-Dependent Changes in Microglia Transcriptional Networks Following Traumatic Brain Injury
Izzy, S., Liu, Q., Fang, Z., Lule, S., Wu, L., Chung, J. Y., Sarro-Schwartz, A., Brown-Whalen, A., Perner, C., Hickman, S. E., et al. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00307 · Cited by 110 · see citing works
Glial Cells and Integrity of the Nervous System
von Bernhardi, R., Eugenín-von Bernhardi, J., Flores, B., & Eugenín León, J. (2016) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-319-40764-7_1 · Cited by 67 · see citing works
The effect of aged microglia on synaptic impairment and its relevance in neurodegenerative diseases
Triviño, J. J., & von Bernhardi, R. (2021) · Neurochemistry International · doi:10.1016/j.neuint.2021.104982 · Cited by 43 · see citing works
Unified theory of Alzheimer’s disease (UTAD): implications for prevention and curative therapy
Nehls, M. (2016) · Journal of Molecular Psychiatry · doi:10.1186/s40303-016-0018-8 · Cited by 41 · see citing works
MicroRNA Profiling in Aging Brain of PSEN1/PSEN2 Double Knockout Mice
Ham, S., Kim, T. K., Lee, S., Tang, Y.-P., & Im, H.-I. (2018) · Molecular Neurobiology · doi:10.1007/s12035-017-0753-6 · Cited by 12 · see citing works
The role of macrophage scavenger receptor 1 (Msr1) in prion pathogenesis
Li, B., Chen, M., Aguzzi, A., & Zhu, C. (2021) · Journal of Molecular Medicine · doi:10.1007/s00109-021-02061-7 · Cited by 7 · see citing works
- Authors
- von Bernhardi, R., Cornejo, F., Parada, G. E., & Eugenín, J.
- Affiliations
- Pontificia Universidad Católica de Chile (CL)
- Universidad de Santiago de Chile (CL)
- Venue
- Frontiers in Cellular Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2015-10-28
- Volume
- 9
- Pages
- 426-426
- ISSN
- 1662-5102 (ISSN-L)
- PMC
- PMC4623426
- OpenAlex
- W2199644913
- Cited by
- 149
- References
- 259
- Citations by year
- 2026: 6 · 2025: 18 · 2024: 24 · 2023: 14 · 2022: 21 · 2021: 17 · 2020: 11 · 2019: 8 · 2018: 11 · 2017: 8 · 2016: 11
- FWCI
- 5.34
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Comisión Nacional de Investigación Científica y Tecnológica
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- Alzheimer's disease, TGF-beta signaling, Smad3, microglial activation, neuroinflammation, aging, neurodegeneration, scavenger receptor A, MSR1, Smad2/3, oxidative stress
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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.
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