Inflammasome inhibition protects dopaminergic neurons from α-synuclein pathology in a model of progressive Parkinson’s disease
Please always quote using this URN: urn:nbn:de:bvb:20-opus-357652
- Neuroinflammation has been suggested as a pathogenetic mechanism contributing to Parkinson’s disease (PD). However, anti-inflammatory treatment strategies have not yet been established as a therapeutic option for PD patients. We have used a human α-synuclein mouse model of progressive PD to examine the anti-inflammatory and neuroprotective effects of inflammasome inhibition on dopaminergic (DA) neurons in the substantia nigra (SN). As the NLRP3 (NOD-, LRR- and pyrin domain-containing 3)-inflammasome is a core interface for both adaptive andNeuroinflammation has been suggested as a pathogenetic mechanism contributing to Parkinson’s disease (PD). However, anti-inflammatory treatment strategies have not yet been established as a therapeutic option for PD patients. We have used a human α-synuclein mouse model of progressive PD to examine the anti-inflammatory and neuroprotective effects of inflammasome inhibition on dopaminergic (DA) neurons in the substantia nigra (SN). As the NLRP3 (NOD-, LRR- and pyrin domain-containing 3)-inflammasome is a core interface for both adaptive and innate inflammation and is also highly druggable, we investigated the implications of its inhibition. Repeat administration of MCC950, an inhibitor of NLRP3, in a PD model with ongoing pathology reduced CD4\(^+\) and CD8\(^+\) T cell infiltration into the SN. Furthermore, the anti-inflammasome treatment mitigated microglial activation and modified the aggregation of α-synuclein protein in DA neurons. MCC950-treated mice showed significantly less neurodegeneration of DA neurons and a reduction in PD-related motor behavior. In summary, early inflammasome inhibition can reduce neuroinflammation and prevent DA cell death in an α-synuclein mouse model for progressive PD.…
Author: | Alexander Grotemeyer, Judith F. Fischer, James B. Koprich, Jonathan M. Brotchie, Robert Blum, Jens Volkmann, Chi Wang Ip |
---|---|
URN: | urn:nbn:de:bvb:20-opus-357652 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Neurologische Klinik und Poliklinik |
Language: | English |
Parent Title (English): | Journal of Neuroinflammation |
Year of Completion: | 2023 |
Volume: | 20 |
Article Number: | 79 |
Source: | Journal of Neuroinflammation (2023) 20:79. https://doi.org/10.1186/s12974-023-02759-0 |
DOI: | https://doi.org/10.1186/s12974-023-02759-0 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | MCC950; NLRP3; Parkinson’s disease; T cells; dopaminergic cells; inflammasome; microglia; movement disorder; neurodegeneration; neuroinflammation |
Release Date: | 2024/05/28 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |