Increased plasma lipocalin‐2 levels are associated with nonmotor symptoms and neuroimaging features in patients with Parkinson's disease

Fan, Yongyan; Li, Xiaohuan; Ma, Jianjun; Yang, Dawei; Liang, Keke; Shen, Yu; Wei, Wei; Dong, Linrui; Liu, Chuanze; She, Zonghan; Qi, Xuelin; Shi, Xiaoxue; Gu, Qi; Zheng, Jinhua; Li, Dongsheng

doi:10.1002/jnr.25303

Cited by 2 publications

(1 citation statement)

References 84 publications

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“…There is accumulating evidence for a strong association between PD and GI disturbances, including intestinal inflammation. Analyses of immune profiles in the stools of PD patients demonstrate higher levels of inflammatory mediators suggestive of GI inflammation (Fan et al, 2024; Hor et al, 2022; Houser et al, 2018; Mulak et al, 2019; Schwiertz et al, 2018). Clinical studies further reveal that people with inflammatory bowel disease and GI infections have an increased risk of developing PD later in life (Fu et al, 2020; Houser et al, 2018; Lee et al, 2021; Liu et al, 2003; Nerius et al, 2020; Shen et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

PINK1 deficiency rewires early immune responses in a mouse model of Parkinson’s disease triggered by intestinal infection

Recinto,

Kazanova,

Bessaiah

et al. 2024

Preprint

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Parkinson’s disease (PD) is characterized by a protracted period of non-motor symptoms, including gastrointestinal (GI) dysfunction, which can precede the development of cardinal motor dysfunction by decades. This long prodrome of disease is highly suggestive of immune cell involvement in the initiation of disease, but currently the field lacks robust modeling systems to study such mechanisms. Pathology may be first initiated in the periphery due to environmental triggers, such as pathogens that enter the GI tract in genetically predisposed individuals. Our group has developed GI-targeted pathogen-induced PD mouse modeling systems (in PINK1 KO mice with gram negative bacterial infections) and found that T cells are a major player in driving PD-like motor symptoms at late stages following infection. Herein, we now map the initiating immune events at the site of infection at the earliest stages with the goal of shedding light on the earliest mechanisms triggering T cell-mediated pathological processes relevant to PD. Using unbiased single cell sequencing, we demonstrate that myeloid cells are the earliest dysregulated immune cell type in PINK1 KO infected mice (at 1-week post-infection) followed by a dysregulated T cell response shortly after (at 2 weeks post-infection). We find that these myeloid cells have an enhanced proinflammatory profile, are more mature, and develop enhanced capacity for antigen presentation. Using unbiased prediction analysis, our data suggests that cytotoxic T cells and myeloid cells are particularly poised for interacting with each other, and we identify possible direct cell-cell interaction pathways that might be implicated. How or if these early aberrant immune responses play a key role in initiating PD autoimmunity is the subject of further investigation.

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