T cell-microglial dialogue in Parkinson's disease and amyotrophic lateral sclerosis: are we listening?
Open accessAbstract
Neuroinflammation is a pathological hallmark in Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), and is characterized by activated microglia and infiltrating T cells at sites of neuronal injury. In PD and ALS, neurons do not die alone; neuronal injury is non-cell-autonomous and depends on a well-orchestrated dialogue in which neuronally secreted misfolded proteins activate microglia and initiate a self-propagating cycle of neurotoxicity. Diverse populations and phenotypes of CD4(+) T cells crosstalk with microglia, and depending on their activation status, influence this dialogue and promote neuroprotection or neurotoxicity. A greater understanding of the T cell population that mediates these effects, as well as the molecular signals involved should provide targets for neuroprotective immunomodulation to treat these devastating neurodegenerative diseases.
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Production of NO and superoxide by activated microglia in PD can cause degeneration of dopaminergic neurons.
“The production of NO and superoxide exerted by activated microglia in PD can cause the degeneration of dopaminergic neurons (Appel et al., 2010).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Appel et al., 2010
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Regulatory Properties of Copolymer I in Th17 Differentiation by Altering STAT3 Phosphorylation
Chen, C., Liu, X., Wan, B., & Zhang, J. Z. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0900193 · Cited by 24 · see citing works
Canh, M.-Y., Serpe, C. J., Sanders, V. M., et al. (2006) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2006.08.006 · Cited by 13 · see citing works
Hensley, K., Floyd, R. A., Gordon, B., et al. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.750886.x · Cited by 10 · see citing works
Langston, J. W., Forno, L. S., Tetrud, J., Reeves, A. G., Kaplan, J. A., & Karluk, D. (1999) · Annals of Neurology · doi:10.1002/1531-8249(199910)46:4 · Cited by 1 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [94]Benoit M 2008 Macrophage polarization in bacterial infections J Immunol 181 3733 3739 18768823
- [95]Dauer W Przedborski S 2003 Parkinson's disease: Mechanisms and Models Neuron 39 889 909 12971891
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Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases
Tang, Y., & Le, W. (2016) · Molecular Neurobiology · doi:10.1007/s12035-014-9070-5 · Cited by 2,190 · see citing works
The role of inflammation in epilepsy
Vezzani, A., French, J., Bartfai, T., & Baram, T. Z. (2011) · Nature Reviews Neurology · doi:10.1038/nrneurol.2010.178 · Cited by 1,876 · see citing works
Neuroinflammation in amyotrophic lateral sclerosis: role of glial activation in motor neuron disease
Philips, T., & Robberecht, W. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(11)70015-1 · Cited by 646 · see citing works
The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma.
Ramirez, A. I., de Hoz, R., Salobrar-Garcia, E., Salazar, J. J., Rojas, B., Ajoy, D., López-Cuenca, I., Rojas, P., Triviño, A., & Ramírez, J. M. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00214 · Cited by 466 · see citing works
Harms, A. S., Cao, S., Rowse, A. L., Thome, A. D., Li, X., Mangieri, L. R., Cron, R. Q., Shacka, J. J., Raman, C., & Standaert, D. G. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.5610-12.2013 · Cited by 406 · see citing works
Yan, Z., Gibson, S. A., Buckley, J. A., Qin, H., & Benveniste, E. N. (2018) · Clinical Immunology · doi:10.1016/j.clim.2016.09.014 · Cited by 318 · see citing works
Inflammatory dysregulation of blood monocytes in Parkinson’s disease patients
Grozdanov, V., Bliederhaeuser, C., Ruf, W. P., Roth, V., Fundel-Clemens, K., Zondler, L., Brenner, D., Martin-Villalba, A., Hengerer, B., Kassubek, J., et al. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1345-4 · Cited by 295 · see citing works
Liu, Z., Qiu, A.-W., Huang, Y., Yang, Y., Chen, J.-N., Gu, T.-T., Cao, B.-B., Qiu, Y.-H., & Peng, Y.-P. (2019) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2019.07.026 · Cited by 207 · 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
Subbarayan, M. S., Hudson, C., Moss, L. D., Nash, K. R., & Bickford, P. C. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01911-4 · Cited by 107 · see citing works
Liu, Z., Huang, Y., Cao, B.-B., Qiu, Y.-H., & Peng, Y.-P. (2017) · Molecular Neurobiology · doi:10.1007/s12035-016-0249-9 · Cited by 112 · see citing works
The Neuroinflammatory Response in ALS: The Roles of Microglia and T Cells
Lewis, C.-A., Manning, J., Rossi, F., & Krieger, C. (2012) · Neurology Research International · doi:10.1155/2012/803701 · Cited by 76 · see citing works
Microglia recapitulate a hematopoietic master regulator network in the aging human frontal cortex
Wehrspaun, C. C., Haerty, W., & Ponting, C. P. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.04.008 · Cited by 64 · see citing works
Liu, Z., Chen, H.-Q., Huang, Y., Qiu, Y.-H., & Peng, Y.-P. (2016) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2015.08.006 · Cited by 51 · see citing works
Gateway reflex: neural activation-mediated immune cell gateways in the central nervous system
Kamimura, D., Ohki, T., Arima, Y., & Murakami, M. (2018) · International Immunology · doi:10.1093/intimm/dxy034 · Cited by 12 · see citing works
- Authors
- Appel, S. H., Beers, D. R., & Henkel, J. S.
- Affiliations
- Houston Methodist (US)
- Venue
- Trends in Immunology
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 31
- Issue
- 1
- Pages
- 7-17
- ISSN
- 1471-4906 (ISSN-L)
- PMC
- PMC4126423
- OpenAlex
- W2034254855
- Cited by
- 256
- References
- 94
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 13 · 2023: 6 · 2022: 5 · 2021: 16 · 2020: 13 · 2019: 15 · 2018: 17 · 2017: 14 · 2016: 23 · 2015: 17 · 2014: 21 · 2013: 20 · 2012: 24
- FWCI
- 1.66
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Trends in Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (NS048950, R01NS048950)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- Parkinson's disease, amyotrophic lateral sclerosis, neuroinflammation, microglia, CD4+ T cells, neurotoxicity, neuroprotection, immunomodulation, neurodegenerative diseases
- MeSH terms
- Amyotrophic Lateral Sclerosis, Animals, Cell Communication, Parkinson Disease, T-Lymphocytes, Microglia, Mice
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 ›
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