Role of enteric glia and microbiota-gut-brain axis in parkinson disease pathogenesis

Santos, Júlio César Claudino dos; Lima, Micael Porto Portela; Brito, Gerly Anne de Castro; Viana, Glauce Socorro de Barros

doi:10.1016/j.arr.2022.101812

Cited by 42 publications

(29 citation statements)

References 167 publications

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“…EECs come into contact with glia 45 and connect to enteric neurons PMID: 25555217 as well as the vagus nerve 41 . It is possible that α-synuclein can spread to enteric glia 70 and thus, provide a potential route for the spread of α-synuclein. It remains to be determined what role glia might have in the spread of α-synuclein to enteric nerves including the vagus that extends beyond the gut.…”

Section: Discussionmentioning

confidence: 99%

Gut mucosal cells transfer α-synuclein to the vagus nerve

Chandra

Sokratian

Chavez

et al. 2023

Preprint

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Epidemiological and histopathological findings have raised the possibility that misfolded alpha-synuclein protein might spread from the gut to the brain and increase the risk of Parkinsons disease (PD). While past experimental studies in mouse models have relied on gut injections of exogenous recombinant alpha-synuclein fibrils to study gut to brain alpha-synuclein transfer, the possible origins of misfolded alpha-synuclein within the gut have remained elusive. We recently demonstrated that sensory cells of the gut mucosa express alpha-synuclein. In this study, we employed mouse intestinal organoids expressing human alpha-synuclein to observe the transfer of alpha-synuclein protein from gut epithelial cells in organoids co-cultured with vagal nodose neurons that are otherwise devoid of alpha-synuclein expression. In intact mice that express pathological human alpha-synuclein, but no mouse alpha;-synuclein, alpha-synuclein fibril templating activity emerges in alpha-synuclein seeded fibril aggregation assays in tissues from the gut, vagus nerve, and dorsal motor nucleus. In newly engineered transgenic mice that restrict pathological human alpha-synuclein expression to intestinal epithelial cells, alpha-synuclein fibril-templating activity transfers to the vagus nerve and to the dorsal motor nucleus. Subdiaphragmatic vagotomy prior to the induction of alpha-synuclein expression in the gut epithelial cells effectively protects the hindbrain from the emergence of alpha-synuclein fibril templating activity. Overall, these findings highlight a novel potential non-neuronal source of fibrillar alpha-synuclein protein that might arise in gut mucosal cells.

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Section: Discussionmentioning

confidence: 99%

Gut mucosal cells transfer α-synuclein to the vagus nerve

Chandra

Sokratian

Chavez

et al. 2023

Preprint

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“…In this regard, the afferent vagus nerve is considered the main retrograde signaling system, bringing information from the gut to the brain. On the other hand, the efferent vagus nerve, containing the cholinergic anti-inflammatory activity, helps control TNF-α and other cytokines secreted by macrophages in the gut [ 221 ]. One common element to all GBA components is the expression of nAChRs that serve myriad roles in this axis ( Figure 2 ).…”

Section: Nachr–microglia and Gut–brain Axismentioning

confidence: 99%

Nicotinic Acetylcholine Receptors in Glial Cells as Molecular Target for Parkinson’s Disease

Soares,

Costa,

Ferrolho

et al. 2024

Cells

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Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by resting tremor, bradykinesia, rigidity, and postural instability that also includes non-motor symptoms such as mood dysregulation. Dopamine (DA) is the primary neurotransmitter involved in this disease, but cholinergic imbalance has also been implicated. Current intervention in PD is focused on replenishing central DA, which provides remarkable temporary symptomatic relief but does not address neuronal loss and the progression of the disease. It has been well established that neuronal nicotinic cholinergic receptors (nAChRs) can regulate DA release and that nicotine itself may have neuroprotective effects. Recent studies identified nAChRs in nonneuronal cell types, including glial cells, where they may regulate inflammatory responses. Given the crucial role of neuroinflammation in dopaminergic degeneration and the involvement of microglia and astrocytes in this response, glial nAChRs may provide a novel therapeutic target in the prevention and/or treatment of PD. In this review, following a brief discussion of PD, we focus on the role of glial cells and, specifically, their nAChRs in PD pathology and/or treatment.

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“…The relationship between the gut microbiota and PD has received increasing attention in recent years. , Dysbiosis may lead to increased permeability of the intestinal epithelium, decreased intestinal barrier function, invasion of pathogenic bacteria or toxins into the intestinal epithelium, activation of intestinal immune cells, stimulation of the secretion of inflammatory factors, resulting in intestinal inflammation and accumulation of abnormal α-synuclein, these abnormal signals spread through the circulatory system and the vagus nerve to the brain, causing damage to dopaminergic neurons in the striatum, further activating neuroinflammation and triggering PD. , Hydroxycinnamic acid derivatives can regulate intestinal flora and, thus, may have a potential protective role in the development of PD.…”

Section: Pharmacological Effects Of Hydroxycinnamic Acid Derivatives:...mentioning

confidence: 99%

The Therapeutic Potential of Hydroxycinnamic Acid Derivatives in Parkinson’s Disease: Focus on In Vivo Research Advancements

Yang

Nao

Dong

2023

J. Agric. Food Chem.

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Hydroxycinnamic acid derivatives (HCDs) are polyphenols that are abundant in cereals, coffee, tea, wine, fruits, vegetables, and other plant-based foods. To aid in the clinical prevention and treatment of Parkinson’s disease (PD), we evaluated in vivo investigations of the pharmacological properties of HCDs relevant to PD, and their pharmacokinetic and safety aspects. An extensive search of published journals was conducted using several literature databases, including PubMed, Google Scholar, and the Web of Science. The search terms included “hydroxycinnamic acid derivatives,” “ferulic acid,” “caffeic acid,” “sinapic acid,” “p-coumaric acid,” “Parkinson’s disease,” and combinations of these keywords. As of April 2023, 455 preclinical studies were retrieved, of which 364 were in vivo studies; we included 17 of these articles on the pharmaceutics of HCDs in PD. Available evidence supports the protective effects of HCDs in PD due to their anti-inflammatory, antioxidant, as well as antiapoptotic physiological activities. Studies have identified possible molecular targets and pathways for the protective actions of HCDs in PD. However, the paucity of studies on these compounds in PD, and the risk of toxicity induced with high-dose applications, limits their use. Thus, multifaceted studies of HCDs in vitro and in vivo are needed.

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Role of enteric glia and microbiota-gut-brain axis in parkinson disease pathogenesis

Cited by 42 publications

References 167 publications

Gut mucosal cells transfer α-synuclein to the vagus nerve

Gut mucosal cells transfer α-synuclein to the vagus nerve

Nicotinic Acetylcholine Receptors in Glial Cells as Molecular Target for Parkinson’s Disease

The Therapeutic Potential of Hydroxycinnamic Acid Derivatives in Parkinson’s Disease: Focus on In Vivo Research Advancements

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