Interaction of an α-synuclein epitope with HLA-DRB1^∗15:01 triggers enteric features in mice reminiscent of prodromal Parkinson's disease.

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-syn_32-46, binds with strong affinity to the HLA-DRB1^∗15:01 allele implicated in autoimmune diseases. We report that α-syn_32-46 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-Syn_32-46 immunization activates innate and adaptive immune gene signatures in the gut and induces changes in the CD4⁺ T_H1/T_H17 trans

SUBMITTER: Garretti F 

PROVIDER: S-EPMC11068096 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature