CD4 T cells mediate brain inflammation and neurodegeneration in a mouse model of Parkinson's disease.
Gregory P. Williams,Aubrey M Schonhoff,Asta Jurkuvenaite,Nicole J Gallups,David G. Standaert,Ashley S. Harms +5 more
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In this paper, the authors found that α-synuclein overexpression in the midbrain of mice leads to the upregulation of the major histocompatibility complex II (MHCII) protein on CNS myeloid cells as well as the infiltration of IFNγ producing CD4 and CD8 T cells into the CNS.Abstract:
α-Synuclein, a key pathological component of Parkinson's disease, has been implicated in the activation of the innate and adaptive immune system. This immune activation includes microgliosis, increased inflammatory cytokines, and the infiltration of T cells into the CNS. More recently, peripherally circulating CD4 and CD8 T cells derived from individuals with Parkinson's disease have been shown to produce Th1/Th2 cytokines in response to α-synuclein, suggesting there may be a chronic memory T cell response present in Parkinson's disease. To understand the potential effects of these α-syn associated T cell responses we used an α-synuclein overexpression mouse model, T cell-deficient mice, and a combination of immunohistochemistry and flow cytometry. In this study, we found that α-synuclein overexpression in the midbrain of mice leads to the upregulation of the major histocompatibility complex II (MHCII) protein on CNS myeloid cells as well as the infiltration of IFNγ producing CD4 and CD8 T cells into the CNS. Interestingly, genetic deletion of TCRβ or CD4, as well as the use of the immunosuppressive drug fingolimod, were able to reduce the CNS myeloid MHCII response to α-synuclein. Furthermore, we observed that CD4-deficient mice were protected from the dopaminergic cell loss observed due to α-syn overexpression. These results suggest that T cell responses associated with α-synuclein pathology may be damaging to key areas of the CNS in Parkinson's disease and that targeting these T cell responses could be an avenue for disease modifying treatments.read more
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Neuroinflammation in Parkinson’s Disease – Putative Pathomechanisms and Targets for Disease-Modification
TL;DR: The possible contribution of interconnected pathways related to the immune response, focusing on the pathophysiology and neurodegeneration of PD, is discussed and an overview of clinical trials targeting neuroinflammation in PD is provided.
Journal ArticleDOI
Upregulation of α-synuclein following immune activation: Possible trigger of Parkinson's disease
TL;DR: In this article , the role of α-synuclein (α-syn) in the immune response to pathogens has been investigated and shown to play a role in the development of synucleinopathies.
Journal ArticleDOI
Neurodegeneration by α-synuclein-specific T cells in AAV-A53T-α-synuclein Parkinson’s disease mice
Akua A. Karikari,Rhonda L. McFleder,Eliana Ribechini,Robert Blum,Valentin Bruttel,Susanne Knorr,Mona Gehmeyr,Jens Volkmann,Jonathan M. Brotchie,Fadhil Ahsan,Beatrice Haack,Camelia M. Monoranu,Ursula Keber,Rima Yeghiazaryan,Axel Pagenstecher,Tobias Heckel,Thorsten Bischler,Jörg Wischhusen,James B. Koprich,Manfred B. Lutz,Chi Wang Ip +20 more
TL;DR: In this article , the functional relevance of α-synuclein-specific immune responses in Parkinson's disease in a mouse model was addressed, where an Adeno-associated vector 1/2 serotype (AAV1/2) expressing human mutated A53T-α-Synuclein was stereotactically injected into the substantia nigra (SN) of either wildtype C57BL/6 or Recombination-activating gene 1 (RAG1)-/- mice.
Journal ArticleDOI
T-cell dysregulation is associated with disease severity in Parkinson's Disease.
Divisha Bhatia,Veselin Grozdanov,Wolfgang Ruf,Jan Kassubek,Albert C. Ludolph,Albert C. Ludolph,Jochen H. Weishaupt,Jochen H. Weishaupt,Karin M Danzer,Karin M Danzer +9 more
TL;DR: In this paper, a detailed look at T-cell numbers, gene expression and activation in cross-sectional cohorts of Parkinson's disease patients and age-matched healthy controls by means of flow cytometry and NanoString gene expression assay was conducted.
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The Positive Role and Mechanism of Herbal Medicine in Parkinson's Disease.
Rong Yin,Jie Xue,Yanfeng Tan,Chuantao Fang,Chunchun Hu,Qian Yang,Xinyu Mei,Dashi Qi,Dashi Qi +8 more
TL;DR: Wang et al. as mentioned in this paper summarized the pathogenic factors of Parkinson's disease including protein aggregation, mitochondrial dysfunction, ion accumulation, neuroinflammation, and oxidative stress, and the related recent advances.
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