Regulation of the neurodegenerative process associated to Parkinson's disease by CD4+ T-cells
Abstract
Neuroinflammation constitutes a fundamental process involved in the physiopathology of Parkinson's disease (PD). Microglial cells play a central role in the outcome of neuroinflammation and consequent neurodegeneration of dopaminergic neurons in the substantia nigra. Current evidence indicates that CD4+ T-cells infiltrate the central nervous system (CNS) in PD, where they play a critical role determining the functional phenotype of microglia, thus regulating the progression of the neurodegenerative process. Here, we first analysed the pathogenic role of inflammatory phenotypes and the beneficial role of anti-inflammatory phenotypes of encephalitogenic CD4+ T-cells involved in the physiopathology of PD. Next, we discussed how alterations of neurotransmitter levels observed in the basal ganglia throughout the time course of PD progression could be strongly affecting the behaviour of encephalitogenic CD4+ T-cells and thereby the outcome of the neuroinflammatory process and the consequent neurodegeneration of dopaminergic neurons. Afterward, we integrated the evidence indicating the involvement of an antigen-specific immune response mediated by T-cells and B-cells against CNS-derived self-constituents in PD. Consistent with the involvement of a relevant autoimmune component in PD, we also reviewed the polymorphisms of both, class I and class II major histocompatibility complexes, associated to the risk of PD. Overall, this study gives an overview of how an autoimmune component involved in PD plays a fundamental role in the progression of the neurodegenerative process.
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MHC-II expression in microglia can play an important role in innate and adaptive immune responses in PD.
“The MHC-II expression in microglia cells can play an important role in the immune responses (innate and adaptive) in PD (Michelucci et al., 2009; Harms et al., 2013; Gonzalez et al., 2015).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Gonzalez et al., 2015
Overexpression of α-syn can induce MHC-II expression by microglia.
“In vivo and in vitro studies have demonstrated that overexpression of α-syn can induce the MHC-II expression by microglia.”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Gonzalez et al., 2015
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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
Iba, M., Kim, C., Sallin, M., Kwon, S., Verma, A., Overk, C., Rissman, R. A., Sen, R., Sen, J. M., & Masliah, E. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01888-0 · Cited by 120 · see citing works
RetractedCD47 in the Brain and Neurodegeneration: An Update on the Role in Neuroinflammatory Pathways
Gheibihayat, S. M., Cabezas, R., Nikiforov, N. G., Jamialahmadi, T., Johnston, T. P., & Sahebkar, A. (2021) · Molecules · doi:10.3390/molecules26133943 · Cited by 34 · see citing works
- Authors
- González, H., Contreras, F., & Pacheco, R.
- Affiliations
- Fundación Ciencia and Vida (CL)
- Universidad Andrés Bello (CL)
- Corresponding author
- Pacheco, Rodrigo
- Venue
- Journal of Neuroimmune Pharmacology
- Published
- 2015-05-28
- Volume
- 10
- Issue
- 4
- Pages
- 561-575
- ISSN
- 1557-1890 (ISSN-L)
- 1557-1904
- OpenAlex
- W373459504
- Cited by
- 70
- References
- 142
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 7 · 2023: 8 · 2022: 8 · 2021: 10 · 2020: 11 · 2019: 9 · 2018: 1 · 2017: 3 · 2016: 3 · 2015: 1
- FWCI
- 0.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Neuroimmune Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Comisión Nacional de Investigación Científica y Tecnológica
- Fondo Nacional de Desarrollo Científico y Tecnológico
- 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, CD4+ T cells, neuroinflammation, microglia, substantia nigra, encephalitogenic T cells, neurotransmitter alterations, basal ganglia, autoimmunity, MHC class I, MHC class II, genetic polymorphism
- MeSH terms
- Animals, Humans, Inflammation, Synaptic Transmission, Parkinson Disease, CD4-Positive T-Lymphocytes, Autoimmunity
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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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