Paraquat exposure induces Parkinsonism by altering lipid profile and evoking neuroinflammation in the midbrain

Tong, Tong; Duan, Weixia; Xu, You‐Ping; Hong, Huihui; Xu, Jia; Fu, Guanyan; Wang, Xue; Yang, Lingling; Deng, Ping; Zhang, Jingjing; He, Haotian; Mao, Gaofeng; Lu, Yuan-Qiang; Lin, Xiaona; Yu, Zhengping; Pi, Huifeng; Cheng, Yong; Xu, Shangcheng; Zhou, Zhou

doi:10.1016/j.envint.2022.107512

Cited by 24 publications

(3 citation statements)

References 48 publications

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“…Environmental exposure to toxins, mainly pesticides, has been long linked with PD, with a meta-analysis finding a 66% increased risk of developing PD after pesticide exposure [51]. Pesticides like paraquat and rotenone, have direct toxic effects by interfering with mitochondrial function, but have also been shown to activate inflammatory pathways, like cytokine release and microgliosis [52,53].…”

Section: Inflammation and Etiology Of Pdmentioning

confidence: 99%

Do Bacterial Outer Membrane Vesicles Contribute to Chronic Inflammation in Parkinson’s Disease?

Koukoulis,

Beauchamp,

Kaparakis-Liaskos

et al. 2024

Journal of Parkinson’s Disease

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Parkinson’s disease (PD) is an increasingly common neurodegenerative disease. It has been suggested that the etiology of idiopathic PD is complex and multifactorial involving environmental contributions, such as viral or bacterial infections and microbial dysbiosis, in genetically predisposed individuals. With advances in our understanding of the gut-brain axis, there is increasing evidence that the intestinal microbiota and the mammalian immune system functionally interact. Recent findings suggest that a shift in the gut microbiome to a pro-inflammatory phenotype may play a role in PD onset and progression. While there are links between gut bacteria, inflammation, and PD, the bacterial products involved and how they traverse the gut lumen and distribute systemically to trigger inflammation are ill-defined. Mechanisms emerging in other research fields point to a role for small, inherently stable vesicles released by Gram-negative bacteria, called outer membrane vesicles in disease pathogenesis. These vesicles facilitate communication between bacteria and the host and can shuttle bacterial toxins and virulence factors around the body to elicit an immune response in local and distant organs. In this perspective article, we hypothesize a role for bacterial outer membrane vesicles in PD pathogenesis. We present evidence suggesting that these outer membrane vesicles specifically from Gram-negative bacteria could potentially contribute to PD by traversing the gut lumen to trigger local, systemic, and neuroinflammation. This perspective aims to facilitate a discussion on outer membrane vesicles in PD and encourage research in the area, with the goal of developing strategies for the prevention and treatment of the disease.

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Section: Inflammation and Etiology Of Pdmentioning

confidence: 99%

Do Bacterial Outer Membrane Vesicles Contribute to Chronic Inflammation in Parkinson’s Disease?

Koukoulis,

Beauchamp,

Kaparakis-Liaskos

et al. 2024

Journal of Parkinson’s Disease

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“…The increase of PLA2 activity has been associated with apoptotic effects [ 230 ], and it has been reported that 6-OHDA induces PLA2 activity within the nigrostriatal tract [ 216 , 231 ]. More recently, a lipidome analysis using ultrahigh-performance liquid chromatography combined with high-resolution mass spectrometry (UHPLC-MS/MS) was used to evaluate changes in the lipidome of the midbrain after paraquat exposure in mice [ 227 ]. In this study, the authors found 35 significantly elevated lipids and 18 remarkably decreased lipids.…”

Section: Lipidomics As a New Tool To Identify Biomarkers In Parkinson...mentioning

confidence: 99%

“…Interestingly, these findings correlated well with motor deficits and alterations in mRNA expression of genes involved in ceramide metabolism in the midbrain. Furthermore, the authors found elevated levels of proinflammatory cytokines in the serum of both mice and humans exposed to this pollutant, suggesting an occurrence of systemic inflammation underlying paraquat-induced neurotoxicity [ 227 ].…”

Section: Lipidomics As a New Tool To Identify Biomarkers In Parkinson...mentioning

confidence: 99%

New Pieces for an Old Puzzle: Approaching Parkinson’s Disease from Translatable Animal Models, Gut Microbiota Modulation, and Lipidomics

et al. 2023

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Parkinson’s disease (PD) is a severe neurodegenerative disease characterized by disabling motor alterations that are diagnosed at a relatively late stage in its development, and non-motor symptoms, including those affecting the gastrointestinal tract (mainly constipation), which start much earlier than the motor symptoms. Remarkably, current treatments only reduce motor symptoms, not without important drawbacks (relatively low efficiency and impactful side effects). Thus, new approaches are needed to halt PD progression and, possibly, to prevent its development, including new therapeutic strategies that target PD etiopathogeny and new biomarkers. Our aim was to review some of these new approaches. Although PD is complex and heterogeneous, compelling evidence suggests it might have a gastrointestinal origin, at least in a significant number of patients, and findings in recently developed animal models strongly support this hypothesis. Furthermore, the modulation of the gut microbiome, mainly through probiotics, is being tested to improve motor and non-motor symptoms and even to prevent PD. Finally, lipidomics has emerged as a useful tool to identify lipid biomarkers that may help analyze PD progression and treatment efficacy in a personalized manner, although, as of today, it has only scarcely been applied to monitor gut motility, dysbiosis, and probiotic effects in PD. Altogether, these new pieces should be helpful in solving the old puzzle of PD.

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The tightest self-assembled ruthenium metal–organic framework combined with proximity hybridization for ultrasensitive electrochemiluminescence analysis of paraquat

Qin,

Liang,

Yang

et al. 2024

Anal Bioanal Chem

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Paraquat exposure induces Parkinsonism by altering lipid profile and evoking neuroinflammation in the midbrain

Cited by 24 publications

References 48 publications

Do Bacterial Outer Membrane Vesicles Contribute to Chronic Inflammation in Parkinson’s Disease?

Do Bacterial Outer Membrane Vesicles Contribute to Chronic Inflammation in Parkinson’s Disease?

New Pieces for an Old Puzzle: Approaching Parkinson’s Disease from Translatable Animal Models, Gut Microbiota Modulation, and Lipidomics

The tightest self-assembled ruthenium metal–organic framework combined with proximity hybridization for ultrasensitive electrochemiluminescence analysis of paraquat

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