Bidirectional gut-to-brain and brain-to-gut propagation of synucleinopathy in non-human primates

Arotcarena, Marie-Laure; Doveró, Sandra; Prigent, Annick; Bourdenx, Mathieu; Camus, Sandrine; Porras, Grégory; Thiolat, Marie-Laure; Tasselli, Maddalena; Arnaúd, Philippe; Kruse, Niels; Mollenhauer, Brit; Trigo‐Damas, Inés; Estrada, Cristina; García‐Carrillo, Nuria; Vaikath, Nishant N.; El-Agnaf, Omar M. A.; Herrero, María Trinidad; Vila, Miquel; Obeso, José A.; Derkinderen, Pascal; Dehay, Benjamin; Bézard, Erwan

doi:10.1093/brain/awaa096

Cited by 149 publications

(109 citation statements)

References 28 publications

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“…[2][3][4][5][6] This "brain-first"/"body-first" division is supported primarily by animal models demonstrating bidirectional extension between the gut and the brain of alpha-synuclein pathology along sympathetic and parasympathetic pathways. 6,7 This most recent study by Horsager and colleagues suggests that some patients exhibit significantly more peripheral organ pathology at the time of initial assessment than others. Although the subtype hypothesis was not proposed as a panacea to explain all of the clinical and pathological variability of PD, there is need for a critical appraisal of its validity and utility in explaining the heterogeneity and individual complexity of PD and informing the direction of future research.…”

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confidence: 98%

The Logic and Pitfalls of Parkinson's Disease as “Brain‐First” Versus “Body‐First” Subtypes

2021

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mentioning

confidence: 98%

The Logic and Pitfalls of Parkinson's Disease as “Brain‐First” Versus “Body‐First” Subtypes

2021

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“…However, studies by one group found that the pathology failed to progress past the dorsal motor nucleus (149,150). Another group injected baboons with patient-derived Lewy body extracts and found that pathology spread to the central nervous system through circulation rather than via the vagus nerve (151). Regardless, there is mounting evidence indicating that bacterial amyloids such as curli, present at high levels in biofilms in the gut, are capable of cross-seeding αSyn aggregation and that αSyn aggregates are capable of spreading from the gut to the brain as a possible initiating event in PD (112,127,134,139,(146)(147)(148)151).…”

Section: Neurological Diseasesmentioning

confidence: 99%

Microbiome or Infections: Amyloid-Containing Biofilms as a Trigger for Complex Human Diseases

et al. 2021

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The human microbiota is the community of microorganisms that live upon or within their human host. The microbiota consists of various microorganisms including bacteria, fungi, viruses, and archaea; the gut microbiota is comprised mostly of bacteria. Many bacterial species within the gut microbiome grow as biofilms, which are multicellular communities embedded in an extracellular matrix. Studies have shown that the relative abundances of bacterial species, and therefore biofilms and bacterial byproducts, change during progression of a variety of human diseases including gastrointestinal, autoimmune, neurodegenerative, and cancer. Studies have shown the location and proximity of the biofilms within the gastrointestinal tract might impact disease outcome. Gram-negative enteric bacteria secrete the amyloid curli, which makes up as much as 85% of the extracellular matrix of enteric biofilms. Curli mediates cell-cell attachment and attachment to various surfaces including extracellular matrix components such as fibronectin and laminin. Structurally, curli is strikingly similar to pathological and immunomodulatory human amyloids such as amyloid-β, which has been implicated in Alzheimer's disease, α-synuclein, which is involved in Parkinson's disease, and serum amyloid A, which is secreted during the acute phase of inflammation. The immune system recognizes both bacterial amyloid curli and human amyloids utilizing the same receptors, so curli also induces inflammation. Moreover, recent work indicates that curli can participate in the self-assembly process of pathological human amyloids. Curli is found within biofilms of commensal enteric bacteria as well as invasive pathogens; therefore, evidence suggests that curli contributes to complex human diseases. In this review, we summarize the recent findings on how bacterial biofilms containing curli participate in the pathological and immunological processes in gastrointestinal diseases, systemic autoimmune diseases, and neurodegenerative diseases.

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“…The levels of a-syn in the blood of baboons injected were increased, which was positively correlated with the levels of a-syn in ENS. Endogenous a-syn may be transmitted long-distance and bidirectional between ENS and the brain through the circulatory system (Arotcarena et al, 2020).…”

Section: Microbiota-targeted Intervention Strategies To Manage Pdmentioning

confidence: 99%

Gut Microbiota Approach—A New Strategy to Treat Parkinson’s Disease

Liu

Nie

et al. 2020

Front. Cell. Infect. Microbiol.

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Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by neuronal loss and dysfunction of dopaminergic neurons located in the substantia nigra, which contain a variety of misfolded a-synuclein (a-syn). Medications that increase or substitute for dopamine can be used for the treatment of PD. Recently, numerous studies have shown gut microbiota plays a crucial role in regulating and maintaining multiple aspects of host physiology including host metabolism and neurodevelopment. In this review article, the role of gut microbiota in the etiological mechanism of PD will be reviewed. Furthermore, we discussed current pharmaceutical medicine-based methods to prevent and treat PD, followed by describing specific strains that affect the host brain function through the gut-brain axis. We explained in detail how gut microbiota directly produces neurotransmitters or regulate the host biosynthesis of neurotransmitters. The neurotransmitters secreted by the intestinal lumen bacteria may induce epithelial cells to release molecules that, in turn, can regulate neural signaling in the enteric nervous system and subsequently control brain function and behavior through the brain-gut axis. Finally, we proved that the microbial regulation of the host neuronal system. Endogenous a-syn can be transmitted long distance and bidirectional between ENS and brain through the circulatory system which gives us a new option that the possibility of altering the community of gut microbiota in completely new medication option for treating PD.

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Bidirectional gut-to-brain and brain-to-gut propagation of synucleinopathy in non-human primates

Cited by 149 publications

References 28 publications

The Logic and Pitfalls of Parkinson's Disease as “Brain‐First” Versus “Body‐First” Subtypes

The Logic and Pitfalls of Parkinson's Disease as “Brain‐First” Versus “Body‐First” Subtypes

Microbiome or Infections: Amyloid-Containing Biofilms as a Trigger for Complex Human Diseases

Gut Microbiota Approach—A New Strategy to Treat Parkinson’s Disease

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