Screening of innate immune receptors in neurodegenerative diseases: A similar pattern
Open accessAbstract
In Alzheimer's disease (AD), Parkinson's disease (PD), dementia with Lewy bodies (DLB) and amyotrophic lateral sclerosis (ALS), neuroinflammatory responses are considered to contribute to neuronal injury. Recently, the innate immune receptors, toll-like receptors (TLRs) and the LPS receptor (CD14) have been related to neurodegeneration. In this study, we systematically assessed the expression of most TLRs and CD14 in AD, PD/DLB and ALS using murine models of these diseases and human post-mortem brain tissues. A common upregulation of TLR2 and CD14 was found in all three animal models. While these two receptors could also be detected in AD patient tissues, they were absent from DLB and ALS tissues. This uniform pattern of innate immune response in animal models of neurodegenerative diseases clearly indicates that this response is part of a non-specific neuroinflammatory effector phase rather than a disease-specific event. The less dynamic disease progression in humans and the location (extracellular versus intracellular) of the aggregated proteins deposits might explain the divergent results seen between animal models and human tissues.
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TLR9 is overexpressed in the spinal cord of an ALS mouse model.
“as well as in the spinal cord of an ALS mouse model.317”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [317]
TLR2 and TLR7 have been shown to display profoundly increased expression levels in APP transgenic mice that accumulate amyloid deposits in their brain.
“Interestingly TLR2, and TLR7 which was also up-regulated in our prion model, has also been shown to display profoundly increased expression levels in APP transgenic mice that accumulate amyloid deposits in their brain [40].”
From MicroRNA 146a (miR-146a) Is Over-Expressed during Prion Disease and Modulates the Innate Immune Response and the Microglial Activation State (2012) · cites this paper as [40]
Cites
Intrahippocampal LPS injections reduce Aβ load in APP+PS1 transgenic mice
DiCarlo, G. (2001) · Neurobiology of Aging · doi:10.1016/s0197-4580(01)00292-5 · Cited by 223 · see citing works
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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
Role of neuroinflammation in neurodegeneration development
Zhang, W., Xiao, D., Mao, Q., & Xia, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01486-5 · Cited by 1,668 · see citing works
“TLR9 was found to be overexpressed in the substantia nigra and putamen of PD patients and in striatum of a PD mouse model,(316) as well as in the spinal cord of an ALS mouse model.(317) DNA derived from degenerating neurons evokes NF-κB activation in microglia via TLR9.”
BackgroundKim, C., Ho, D.-H., Suk, J.-E., You, S., Michael, S., Kang, J., Joong Lee, S., Masliah, E., Hwang, D., Lee, H.-J., et al. (2013) · Nature Communications · doi:10.1038/ncomms2534 · Cited by 856 · see citing works
Toll‐like receptor 4 is required for α‐synuclein dependent activation of microglia and astroglia
Fellner, L., Irschick, R., Schanda, K., Reindl, M., Klimaschewski, L., Poewe, W., Wenning, G. K., & Stefanova, N. (2013) · Glia · doi:10.1002/glia.22437 · Cited by 697 · see citing works
González, H., Elgueta, D., Montoya, A., & Pacheco, R. (2014) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2014.07.012 · Cited by 352 · see citing works
Toll-like receptors in the pathogenesis of neuroinflammation
Kumar, V. (2019) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2019.03.012 · Cited by 331 · see citing works
Role of Microglia TLRs in Neurodegeneration
Fiebich, B. L., Batista, C. R. A., Saliba, S. W., Yousif, N. M., & de Oliveira, A. C. P. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00329 · Cited by 291 · see citing works
Extracellular mutant SOD1 induces microglial‐mediated motoneuron injury
Zhao, W., Beers, D. R., Henkel, J. S., Zhang, W., Urushitani, M., Julien, J., & Appel, S. H. (2010) · Glia · doi:10.1002/glia.20919 · Cited by 288 · see citing works
Toll-Like Receptor 4 Promotes α-Synuclein Clearance and Survival of Nigral Dopaminergic Neurons
Stefanova, N., Fellner, L., Reindl, M., Masliah, E., Poewe, W., & Wenning, G. K. (2011) · The American Journal of Pathology · doi:10.1016/j.ajpath.2011.04.013 · Cited by 272 · see citing works
Dual Roles for Perivascular Macrophages in Immune-to-Brain Signaling
Serrats, J., Schiltz, J. C., García-Bueno, B., van Rooijen, N., Reyes, T. M., & Sawchenko, P. E. (2010) · Neuron · doi:10.1016/j.neuron.2009.11.032 · Cited by 253 · see citing works
Microglial Aβ Receptors in Alzheimer’s Disease
Yu, Y., & Ye, R. D. (2015) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-014-0101-6 · Cited by 247 · see citing works
Toll-like receptor signaling in amyotrophic lateral sclerosis spinal cord tissue
Casula, M., Iyer, A. M., Spliet, W. G. M., Anink, J. J., Steentjes, K., Sta, M., Troost, D., & Aronica, E. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.02.001 · Cited by 200 · see citing works
Toll-like receptors in the depressed and suicide brain
Pandey, G. N., Rizavi, H. S., Ren, X., Bhaumik, R., & Dwivedi, Y. (2014) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2014.01.021 · Cited by 164 · see citing works
Drouin-Ouellet, J., St-Amour, I., Saint-Pierre, M., Lamontagne-Proulx, J., Kriz, J., Barker, R. A., & Cicchetti, F. (2015) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyu103 · Cited by 153 · see citing works
Saba, R., Gushue, S., Huzarewich, R. L. C. H., Manguiat, K., Medina, S., Robertson, C., & Booth, S. A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030832 · Cited by 151 · see citing works
Targeting innate immunity for neurodegenerative disorders of the central nervous system
Andreasson, K. I., Bachstetter, A. D., Colonna, M., Ginhoux, F., Holmes, C., Lamb, B., Landreth, G., Lee, D. C., Low, D., Lynch, M. A., et al. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13667 · Cited by 126 · see citing works
Scheiblich, H., Bousset, L., Schwartz, S., Griep, A., Latz, E., Melki, R., & Heneka, M. T. (2021) · The Journal of Immunology · doi:10.4049/jimmunol.2100035 · Cited by 122 · see citing works
McDonald, C. L., Hennessy, E., Rubio-Araiz, A., Keogh, B., McCormack, W., McGuirk, P., Reilly, M., & Lynch, M. A. (2016) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2016.07.143 · Cited by 108 · see citing works
The role of the immune system in neurodegenerative disorders: Adaptive or maladaptive?
Doty, K. R., Guillot-Sestier, M.-V., & Town, T. (2015) · Brain Research · doi:10.1016/j.brainres.2014.09.008 · Cited by 104 · see citing works
Non-cell-autonomous Neurotoxicity of α-synuclein Through Microglial Toll-like Receptor 2
Kim, C., Lee, H.-J., Masliah, E., & Lee, S.-J. (2016) · Experimental Neurobiology · doi:10.5607/en.2016.25.3.113 · Cited by 92 · see citing works
Zhou, X., Yuan, L., Zhao, X., Hou, C., Ma, W., Yu, H., & Xiao, R. (2014) · Nutrition · doi:10.1016/j.nut.2013.06.006 · Cited by 89 · see citing works
Masitinib for the treatment of mild to moderate Alzheimer’s disease
Folch, J., Petrov, D., Ettcheto, M., Pedrós, I., Abad, S., Beas-Zarate, C., Lazarowski, A., Marin, M., Olloquequi, J., Auladell, C., et al. (2015) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.2015.1045419 · Cited by 80 · see citing works
De Paola, M., Mariani, A., Bigini, P., Peviani, M., Ferrara, G., Molteni, M., Gemma, S., Veglianese, P., Castellaneta, V., Boldrin, V., et al. (2012) · Molecular Medicine · doi:10.2119/molmed.2012.00020 · Cited by 75 · see citing works
Regulation of the neurodegenerative process associated to Parkinson's disease by CD4+ T-cells
González, H., Contreras, F., & Pacheco, R. (2015) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-015-9618-9 · Cited by 70 · see citing works
Han, S.-H., Park, J.-C., & Mook-Jung, I. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2015.12.004 · Cited by 67 · see citing works
Wang, S., Zhang, X., Zhai, L., Sheng, X., Zheng, W., Chu, H., & Zhang, G. (2018) · Journal of Molecular Neuroscience · doi:10.1007/s12031-018-1032-3 · Cited by 52 · see citing works
Michaud, J.-P., Richard, K. L., & Rivest, S. (2011) · Molecular Neurodegeneration · doi:10.1186/1750-1326-6-5 · Cited by 48 · see citing works
Acylated Ghrelin as a Multi-Targeted Therapy for Alzheimer's and Parkinson's Disease
Reich, N., & Hölscher, C. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.614828 · Cited by 48 · see citing works
“, 2009), whereas the enhanced transcription of TLR2 and TLR4 have been detected in α-synuclein and MPTP mouse models of PD (Panaro et al., 2008; Letiembre et al., 2009), indicating that immune regulation is harmfully altered in AD and PD.”
BackgroundImmune-mediated processes in neurodegeneration: where do we stand?
Fakhoury, M. (2016) · Journal of Neurology · doi:10.1007/s00415-016-8052-0 · Cited by 43 · see citing works
Screening of Toll-Like Receptors Expression in Multiple System Atrophy Brains
Brudek, T., Winge, K., Agander, T. K., & Pakkenberg, B. (2013) · Neurochemical Research · doi:10.1007/s11064-013-1020-5 · Cited by 43 · see citing works
Absence of CD14 delays progression of prion diseases accompanied by increased microglial activation
Sakai, K., Hasebe, R., Takahashi, Y., Song, C.-H., Suzuki, A., Yamasaki, T., & Horiuchi, M. (2013) · Journal of Virology · doi:10.1128/jvi.02072-13 · Cited by 37 · see citing works
When the infectious environment meets the AD brain
Ganz, T., Fainstein, N., & Ben-Hur, T. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00559-3 · Cited by 39 · see citing works
The role of immune-mediated alterations and disorders in ALS disease
Rodrigues Lima-Junior, J., Sulzer, D., Lindestam Arlehamn, C. S., & Sette, A. (2021) · Human Immunology · doi:10.1016/j.humimm.2021.01.017 · Cited by 33 · see citing works
Ernest James Phillips, T., & Maguire, E. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.652593 · Cited by 33 · see citing works
- Authors
- Letiembre, M., Liu, Y., Walter, S., Hao, W., Pfander, T., Wrede, A., Schulz-Schaeffer, W., & Fassbender, K.
- Affiliations
- Saarland University (DE)
- University of Göttingen (DE)
- Corresponding author
- Fassbender, Klaus
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2009-05
- Volume
- 30
- Issue
- 5
- Pages
- 759-768
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2139463652
- Cited by
- 228
- References
- 1
- Citations by year
- 2025: 5 · 2024: 10 · 2023: 11 · 2022: 15 · 2021: 11 · 2020: 22 · 2019: 12 · 2018: 10 · 2017: 11 · 2016: 11 · 2015: 19 · 2014: 21 · 2013: 14 · 2012: 17
- FWCI
- 4.86
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, other-oa)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- innate immune receptors, Toll-like receptors, CD14, neuroinflammation, neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, amyotrophic lateral sclerosis, TLR2, murine disease models, postmortem brain, protein aggregates
- MeSH terms
- Alzheimer Disease, Amyotrophic Lateral Sclerosis, Animals, Brain, Disease Models, Animal, Encephalitis, Female, Humans, Immunity, Innate, Male, Mice, Inbred C57BL, Mice, Transgenic, Parkinson Disease, Species Specificity, Biomarkers, Up-Regulation, Lipopolysaccharide Receptors, Neurodegenerative Diseases, Lewy Body Disease, Extracellular Fluid, Toll-Like Receptors, Mice
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