TY  - JOUR
A1  - Grotemeyer, Alexander
A1  - Fischer, Judith F.
A1  - Koprich, James B.
A1  - Brotchie, Jonathan M.
A1  - Blum, Robert
A1  - Volkmann, Jens
A1  - Ip, Chi Wang
T1  - Inflammasome inhibition protects dopaminergic neurons from α-synuclein pathology in a model of progressive Parkinson’s disease
T2  - Journal of Neuroinflammation
N2  - 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 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.
KW  - neurodegeneration
KW  - movement disorder
KW  - neuroinflammation
KW  - Parkinson’s disease
KW  - inflammasome
KW  - dopaminergic cells
KW  - NLRP3
KW  - MCC950
KW  - microglia
KW  - T cells
Y1  - 2023
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/35765
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-357652
VL  - 20
ER  -