Matches in SemOpenAlex for { <https://semopenalex.org/work/W4385989451> ?p ?o ?g. }
- W4385989451 abstract "Enteric symptoms are hallmarks of prodromal Parkinson’s disease (PD) that appear decades before the onset of motor symptoms and diagnosis. PD patients possess circulating T cells that recognize specific α-synuclein (α-syn)-derived epitopes. One epitope, α-syn32-46, binds with strong affinity to the HLA-DRB1∗15:01 allele implicated in autoimmune diseases. We report that α-syn32-46 immunization in a mouse expressing human HLA-DRB1∗15:01 triggers intestinal inflammation, leading to loss of enteric neurons, damaged enteric dopaminergic neurons, constipation, and weight loss. α-Syn32-46 immunization activates innate and adaptive immune gene signatures in the gut and induces changes in the CD4+ TH1/TH17 transcriptome that resemble tissue-resident memory (TRM) cells found in mucosal barriers during inflammation. Depletion of CD4+, but not CD8+, T cells partially rescues enteric neurodegeneration. Therefore, interaction of α-syn32-46 and HLA-DRB1∗15:0 is critical for gut inflammation and CD4+ T cell-mediated loss of enteric neurons in humanized mice, suggesting mechanisms that may underlie prodromal enteric PD." @default.
- W4385989451 created "2023-08-19" @default.
- W4385989451 creator A5010966529 @default.
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- W4385989451 creator A5043267221 @default.
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- W4385989451 creator A5086830763 @default.
- W4385989451 date "2023-08-01" @default.
- W4385989451 modified "2023-10-18" @default.
- W4385989451 title "Interaction of an α-synuclein epitope with HLA-DRB1∗15:01 triggers enteric features in mice reminiscent of prodromal Parkinson’s disease" @default.
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- W4385989451 doi "https://doi.org/10.1016/j.neuron.2023.07.015" @default.