JAK1/2 Inhibitor Suppresses Neuroinflammation in the Thy1 α-Syn Mouse Model of Parkinson’s Disease

Abstract Parkinson’s Disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons and accumulation α-synuclein (α-Syn). Targeting JAK/STAT pathway to treat PD under investigation due its roles in inflammatory cytokine production activation immune cells. Striatal injection sonicated human α-Syn pre-formed fibrils (PFF) enhances cell infiltration, phosphorylation MHC Class II expression Thy1 model (Thy1-PD). We investigated effect inhibiting using JAK1/2 inhibitor, AZD1480, on neuroinflammation. Immunofluorescence staining showed significantly decreased Thy1-PD mice after AZD1480 treatment. treatment reduced infiltration CD4 +T-cells, CD8 CD19 +B-cells macrophages into midbrain compared vehicle-treated PFF mice, as assessed flow cytometry. Furthermore, suppressed class +macrophages dendritic cells PFF-injected mice. Importantly, single-cell RNAseq analysis CD45 +cells identified 9 clusters microglia, 5 T-cells, which specific pathogenic T-cells are critical for responses numbers clusters, comparable control monomer/PBS Together, these results suggest suppresses innate adaptive cells, thereby reducing neuroinflammatory response model. This work was supported grant P50NS108675.