CD11c公司
帕金森病
小胶质细胞
α-突触核蛋白
回肠
细胞生物学
生物
免疫系统
炎症
神经科学
神经退行性变
疾病
免疫学
医学
病理
基因
表型
遗传学
内分泌学
作者
Rhonda L. McFleder,A. Makhotkina,Janos Groh,Ursula Keber,Fabian Imdahl,Josefina Peña Mosca,Alina Peteranderl,Jingjing Wu,Sawako Tabuchi,Jan Hoffmann,Ann-Kathrin Karl,Axel Pagenstecher,Jörg Vogel,Andreas Beilhack,James B. Koprich,Jonathan M. Brotchie,Antoine‐Emmanuel Saliba,Jens Volkmann,Chi Wang Ip
标识
DOI:10.1038/s41467-023-43224-z
摘要
Inflammation in the brain and gut is a critical component of several neurological diseases, such as Parkinson's disease (PD). One trigger of the immune system in PD is aggregation of the pre-synaptic protein, α-synuclein (αSyn). Understanding the mechanism of propagation of αSyn aggregates is essential to developing disease-modifying therapeutics. Using a brain-first mouse model of PD, we demonstrate αSyn trafficking from the brain to the ileum of male mice. Immunohistochemistry revealed that the ileal αSyn aggregations are contained within CD11c+ cells. Using single-cell RNA sequencing, we demonstrate that ileal CD11c+ cells are microglia-like and the same subtype of cells is activated in the brain and ileum of PD mice. Moreover, by utilizing mice expressing the photo-convertible protein, Dendra2, we show that CD11c+ cells traffic from the brain to the ileum. Together these data provide a mechanism of αSyn trafficking between the brain and gut.
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