Gut microbiome, short-chain fatty acids, alpha-synuclein, neuroinflammation, and ROS/RNS: Relevance to Parkinson's disease and therapeutic implications

Redox Biology, Год журнала: 2024, Номер 71, С. 103092 - 103092

Опубликована: Фев. 16, 2024

In this review, we explore how short-chain fatty acids (SCFAs) produced by the gut microbiome affect Parkinson's disease (PD) through their modulatory interactions with alpha-synuclein, neuroinflammation, and oxidative stress mediated reactive oxygen nitrogen species (ROS/RNS). particular, SCFAs-such as acetate, propionate, butyrate-are involved in gut-brain communication can modulate alpha-synuclein aggregation, a hallmark of PD. The patients PD has lower levels SCFAs than healthy individuals. Probiotics may be potential strategy to restore alleviate symptoms, but underlying mechanisms are not fully understood. Also discuss present guts brains PD, induce neuroinflammation via ROS/RNS. Alpha-synuclein is considered an early biomarker for link axis pathogenesis. Therefore, elucidating role impact on alpha-synuclein-induced microglia ROS/RNS crucial pathogenesis treatment.

Язык: Английский

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Therapeutics for neurodegenerative diseases by targeting the gut microbiome: from bench to bedside

Translational Neurodegeneration, Год журнала: 2024, Номер 13(1)

Опубликована: Фев. 27, 2024

The aetiologies and origins of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's (PD), amyotrophic lateral sclerosis (ALS) Huntington's (HD), are complex multifaceted. A growing body evidence suggests that the gut microbiome plays crucial roles in development progression diseases. Clinicians have come to realize therapeutics targeting potential halt This narrative review examines alterations AD, PD, ALS HD, highlighting close relationship between brain Processes mediate microbiome-brain communication including immunological, vagus nerve circulatory pathways, evaluated. Furthermore, we summarize for diseases modify its metabolites, diets, probiotics prebiotics, microbial antibacterials faecal transplantation. Finally, current challenges future directions discussed.

Язык: Английский

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Gut microbiota produces biofilm-associated amyloids with potential for neurodegeneration

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Май 16, 2024

Abstract Age-related neurodegenerative diseases involving amyloid aggregation remain one of the biggest challenges modern medicine. Alterations in gastrointestinal microbiome play an active role aetiology neurological disorders. Here, we dissect amyloidogenic properties biofilm-associated proteins (BAPs) gut microbiota and their implications for synucleinopathies. We demonstrate that BAPs are naturally assembled as amyloid-like fibrils insoluble fractions isolated from human microbiota. show BAP genes part accessory genomes, revealing variability. Remarkably, abundance certain is correlated with Parkinson’s disease (PD) incidence. Using cultured dopaminergic neurons Caenorhabditis elegans models, report BAP-derived amyloids induce α-synuclein aggregation. Our results chaperone-mediated autophagy compromised by amyloids. Indeed, inoculation into brains wild-type mice promote key pathological features PD. Therefore, our findings establish use potential targets biomarkers α-synucleinopathies.

Язык: Английский

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

Cells, Год журнала: 2024, Номер 13(6), С. 474 - 474

Опубликована: Март 7, 2024

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

Язык: Английский

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The vagus nerve: An old but new player in brain–body communication

Brain Behavior and Immunity, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 1, 2024

Язык: Английский

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Lewy body diseases and the gut

Molecular Neurodegeneration, Год журнала: 2025, Номер 20(1)

Опубликована: Янв. 30, 2025

Abstract Gastrointestinal (GI) involvement in Lewy body diseases (LBDs) has been observed since the initial descriptions of patients by James Parkinson. Recent experimental and human observational studies raise possibility that pathogenic alpha-synuclein (⍺-syn) might develop GI tract subsequently spread to susceptible brain regions. The cellular mechanistic origins ⍺-syn propagation disease are under intense investigation. Experimental LBD models have implicated important contributions from intrinsic gut microbiome, intestinal immune system, environmental toxicants, acting as triggers modifiers pathologies. Here, we review primary clinical observations link dysfunctions LBDs. We first provide an overview anatomy repertoire relevant for disease, with a focus on luminal-sensing cells epithelium including enteroendocrine express make direct contact nerves. describe interactions within resident microbes exogenous how these may directly contribute pathology along related metabolic immunological responses. Finally, critical knowledge gaps field highlighted, focusing pivotal questions remain some 200 years after dysfunction predict better understanding pathophysiologies influence risk progression will accelerate discoveries lead deeper overall potential therapeutic strategies targeting gut-brain axis delay, arrest, or prevent progression.

Язык: Английский

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Escherichia Coli K1-colibactin meningitis induces microglial NLRP3/IL-18 exacerbating H3K4me3-synucleinopathy in human inflammatory gut-brain axis

Communications Biology, Год журнала: 2025, Номер 8(1)

Опубликована: Март 6, 2025

Escherichia coli K1 (E. K1) meningitis early occurs in the gastrointestinal and causes severe damage to central nervous system, including lifelong neurological complications survivors. However, cellular mechanism by which E. may cause neuropathies is not well understood due lack of relevant human multi-organ models for studying multifaceted systemic inflammation across gut-brain axis. Here, we reconstruct a multicellular model axis identify neuropathogenic driven K1-colibactin meningitis. We observed that K1-genotoxic colibactin induced intestinal peripheral interleukin 6, causing blood-brain barrier injury endothelial via p38/p65 pathways. Serpin-E1 from damaged cerebral endothelia induces reactive astrocytes release IFN-γ, reduces microglial phagocytosis exacerbates detrimental neuroinflammation NLRP3/IL-18 Microglial IL-18 elevates neuronal oxidative stress worsens DNA double-strand breaks K1-infected neurons, leading H3K4 trimethylation phosphorylation alpha-synuclein. Our findings suggest therapeutic strategies post-bacterial treatment potentially prevent initiation synucleinopathy.

Язык: Английский

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The gut-brain vagal axis scales hippocampal memory processes and plasticity

Neurobiology of Disease, Год журнала: 2024, Номер 199, С. 106569 - 106569

Опубликована: Июнь 15, 2024

The vagus nerve serves as an interoceptive relay between the body and brain. Despite its well-established role in feeding behaviors, energy metabolism, cognitive functions, intricate functional processes linking to hippocampus contribution learning memory dynamics remain still elusive. Here, we investigated whether how gut-brain vagal axis contributes hippocampal at behavioral, functional, cellular, molecular levels. Our results indicate that integrity of is essential for long-term recognition memories, while sparing other forms memory. In addition, by combing multi-scale approaches, our findings show tone exerts a permissive scaling intracellular signaling events, gene expressions, dendritic spines density well plasticities (LTD LTP). These highlight critical maintaining spontaneous homeostatic functions ensembles regulating their functions. conclusion, study provides comprehensive insights into multifaceted involvement shaping time-dependent dynamics. Understanding mechanisms underlying this body-brain neuronal communication may pave way novel therapeutic approaches conditions associated with decline, including neurodegenerative disorders.

Язык: Английский

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Microbiota–neuroepithelial signalling across the gut–brain axis

Nature Reviews Microbiology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 2, 2025

Язык: Английский

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The Use of Neurons Derived from Pluripotent Stem Cells to Study Nerve–Cancer Cell Interactions

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3057 - 3057

Опубликована: Март 27, 2025

Tumor innervation is a complex interaction between nerves and cancer cells that consists of axons invading tumors, its complexity remains largely unknown in humans. Although some retrospective studies have provided important insights into the relationship further knowledge required about this biological process. Animal experiments elucidated several molecular cellular mechanisms tumor innervation; however, no experimental models currently exist to study interactions human nerve cells. Human pluripotent stem can differentiate neurons for research purposes; use these with unexplored. Hence, here we analyze potential derived from unravel poorly understood innervation.

Язык: Английский

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