The Gut–Brain Axis Based on α-Synuclein Propagation—Clinical, Neuropathological, and Experimental Evidence

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 3994 - 3994

Published: April 23, 2025

The cytopathological hallmark of Parkinson’s disease (PD) is a neuronal cytoplasmic inclusion called Lewy body (LB). bodies are composed alpha-synuclein (aSyn), 140 aa protein that predominantly expressed in the presynaptic terminal and which implicated neurotransmitter release. Recently, aSyn was found to propagate from neuron trans-synaptic manner. Although precise molecular mechanisms unclear, propagation believed play major role progression pathology PD. Neuropathologically, initial has been shown be formed dorsal motor nucleus vagus (DMV) or olfactory bulb by neuropathological studies. Since DMV innervates enteric nervous system (ENS) LBs gut nerve plexuses, it conceivable then other regions brain. In this article, clinical, neuropathological, experimental evidence supporting negating idea ENS brain leads PD reviewed. Moreover, seeds through systemic circulation multifocal generation discussed as potential alternative scenario for spreading

Language: Английский

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Probiotics as Potential Treatments for Neurodegenerative Diseases: a Review of the Evidence from in vivo to Clinical Trial

Biomolecules & Therapeutics, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Neurodegenerative diseases (NDDs), characterized by the progressive deterioration of structure and function nervous system, represent a significant global health challenge.Emerging research suggests that gut microbiota plays critical role in regulating neurodegeneration via modulation gut-brain axis.Probiotics, defined as live microorganisms confer benefits to host, have garnered attention owing their therapeutic potential NDDs.This review examines current trends related microbiome-gut-brain axis across various NDDs, highlighting key findings implications.Additionally, effects specific probiotic strains, including Lactobacillus plantarum, Bifidobacterium breve, rhamnosus, on neurodegenerative processes were assessed, focusing benefits.Overall, this emphasizes probiotics promising agents for underscoring importance further investigation into emerging field.

Language: Английский

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Oral and gut microbiome profiles in people with early idiopathic Parkinson’s disease

Communications Medicine, Journal Year: 2024, Volume and Issue: 4(1)

Published: Oct. 23, 2024

Early detection of Parkinson's disease (PD), a neurodegenerative with central and peripheral nerve involvement, ensures timely treatment access. Microbes influence nervous system health are altered in PD. We examined gut mouth microbiomes from recently diagnosed patients geographically diverse, matched case-control, shotgun metagenomics study. Here, we show greater alpha-diversity 445 PD versus 221 controls. The microbial signature includes overabundance 16 OTUs, including Streptococcus mutans Bifidobacterium dentium, depletion 28 OTUs. Machine learning models indicate that subspecies level oral microbiome abundances best distinguish reasonably high accuracy (area under the curve: 0.758). Microbial networks disrupted cases, reduced connectivity between short-chain fatty acid-producing bacteria gut. Importantly, diversity metrics associated non-motor autonomic symptom severity. Our results provide evidence predictive signatures could possibly be used as biomarkers for early PD, particularly when there is involvement. Stagaman et al. investigate associations idiopathic (PD) composition both saliva stool large, diverse US cohort. Abundances microbes, Prevotella, Neisseria, controls cases. characterized by motor symptoms, such tremors, constipation. aim was to determine whether were differences number types microbes living intestines people without saw significant communities healthy compared Additionally, found proportions microbe at distinguishing identified specific kinds driving this distinction. These highlight potential importance understanding causes symptomatology

Language: Английский

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Mogroside V and mogrol: unveiling the neuroprotective and metabolic regulatory roles of Siraitia grosvenorii in Parkinson’s disease

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: July 23, 2024

Introduction Siraitia grosvenorii (Swingle) C. Jeffrey, is an edible and traditional medicine widely used in China. Mogroside V (MGV) mogrol (MG) are its main active ingredients, which have been found to be effective the treatment of neurodegenerative diseases recently. However, whether they can effectively treat Parkinson’s disease (PD) their underlying mechanisms not sufficiently explored. In this study, we investigated neuroprotective metabolic regulatory effects MGV MG on PD. Materials methods Using SH-SY5Y cell models MPTP-induced mouse model PD, evaluated compounds’ efficacy mitigating MPP+-induced neurotoxicity ameliorating motor deficits dopaminergic neuron loss. Employing targeted metabolomics bioinformatics analysis investigate Metabolic imbalance rectification caused by treatment. The vivo experimental protocol encompassed a 14-day drug administration regimen with mice randomly allocated into six groups (n = 9) receiving distinct compound dosages including control group, MGV-H (30 mg/kg/day), MGV-L (10 MG-H (15 MG-L (3 mg/kg/day). Results Our findings revealed that pre-treatment significantly enhanced viability cells exposed MPP+, demonstrating potent protective effect against neurotoxicity. MPTP model, MGV-H, MGV-L, coordination as assessed rotarod test ( p < 0.05); evidently inhibited neuronal loss substantia nigra pars compacta 0.05). Furthermore, metabolomic highlighted restoration balance, impacting 160 differential metabolites modulating key pathways disrupted sphingolipid metabolism, fatty acid amino metabolism. Notably, led regulation 106 metabolites, showing recovery trend towards normal levels, constitutes approximately 17.5% identified metabolites. Key such n-acetyl-l-glutamate, hexadecanoic acid, 9-octadecenal were altered 0.05), underscoring broad-spectrum capacity. Conclusion This study underscores potential natural compounds developing comprehensive strategies for diseases, paving way future clinical research validate therapeutic mogrosides

Language: Английский

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Diagnostic accuracy and predictors of alpha-synuclein accumulation in the gastrointestinal tract of Parkinson’s disease

npj Parkinson s Disease, Journal Year: 2024, Volume and Issue: 10(1)

Published: Aug. 15, 2024

The only characteristic of alpha-synuclein (AS) accumulation in the gastrointestinal (GI) tract Parkinson's disease (PD) found pathological studies is "rostrocaudal gradient," which describes more frequent presence AS upper GI than lower tract. This study aimed to determine diagnostic accuracy and identify predictors PD patients. frequency was compared between patients (N = 97) who underwent radical surgery for cancer individually matched controls 94). We evaluated neural structures using phosphorylated immunohistochemistry. A multivariable logistic regression analysis conducted significantly higher (75.3%) (8.5%, p-value < 0.001). sensitivity specificity full-layer evaluation were 75.3% 91.5%, respectively. When confined mucosal/submucosal layer, 46.9% 94.7%, rostrocaudal gradient duration from symptom onset longer with (4.9 ± 4.9 years) without (1.8 4.1 years, 0.005). Both independently predicted Our suggests PD-related follows a temporally increasing but spatially static progression pattern.

Language: Английский

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An in vitro multi-organ microphysiological system (MPS) to investigate the gut-to-brain translocation of neurotoxins

Biomicrofluidics, Journal Year: 2024, Volume and Issue: 18(5)

Published: Sept. 1, 2024

The death of dopamine-producing neurons in the substantia nigra base brain is a defining pathological feature development Parkinson's disease (PD). PD is, however, multi-systemic disease, also affecting peripheral nervous system and gastrointestinal tract (GIT) that interact via gut-brain axis (GBA). Our dual-flow GIT-brain microphysiological (MPS) was modified to investigate gut-to-brain translocation neurotoxin trigger PD, 1-methyl-4-phenylpyridinium (MPP

Language: Английский

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Neuroprotective effects of biogenic silver nanoparticles in Parkinson's disease: In vitro and in vivo study

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: unknown, P. 138236 - 138236

Published: Dec. 1, 2024

The study aimed to develop immunomodulatory silver nanoparticles (CHT-PCT/AgNPs) using a green chemistry approach with Umbilicaria esculenta (U.E.) extract protect neurons from Parkinson's disease. synthesized CHT-PCT/AgNPs measured 88.2 ± 33.7 nm in size, zeta potential of approximately 24.5 1.9 mV. In vitro assays demonstrated that the green-synthesized exhibited greater biocompatibility and antioxidant properties compared chemically AgNPs. MTT assay indicated were cytocompatible up 50 μg/mL, but higher concentrations resulted significant toxicity. DPPH revealed dose-dependent activity, although it was lower than ascorbic acid. animal studies MPTP-induced Parkinsonism, count tyrosine hydroxylase (TH)-positive cells varied across groups, healthy controls showing 145.3 11.0 negative control group only 21.6 4.1. Additionally, number DRD1-positive also reflected similar trend. These findings suggest may serve as neuroprotective agent mitigate

Language: Английский

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Oral and gut microbiome profiles in early Parkinson’s disease

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 11, 2024

Early detection of Parkinson’s disease (PD), a neurodegenerative with central and peripheral nerve involvement, ensures timely treatment access. Microbes influence nervous system health are altered in PD. We examined gut mouth microbiomes from recently diagnosed patients geographically diverse, matched case-control, metagenomics study. demonstrated greater alpha-diversity 464 PD versus 249 controls. The microbial signature included overabundance 16 OTUs, including Streptococcus mutans Bifidobacterium dentium, depletion 28 OTUs. Machine learning models indicated sub-species level oral microbiome abundances best distinguished relatively high accuracy (area under the curve: 0.758). Microbial networks were disrupted cases, reduced connectivity short-chain fatty acid-producing bacteria stool. Microbiome diversity metrics associated non-motor autonomic symptom severity. Our results provide evidence for predictive taxonomic signatures that may be useful early detection, particularly involvement.

Language: Английский

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The Role of Gastrointestinal Dysbiosis and Fecal Transplantation in Various Neurocognitive Disorders

Cureus, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 26, 2024

This review explores the critical role of human microbiome in neurological and neurodegenerative disorders, focusing on gut-brain axis dysfunction caused by dysbiosis, an imbalance gut bacteria. Dysbiosis has been linked to diseases such as Alzheimer's disease, Parkinson's disease (PD), multiple sclerosis (MS), stroke. The influences central nervous system (CNS) through signaling molecules, including short-chain fatty acids, neurotransmitters, metabolites, impacting brain health progression. Emerging therapies, fecal microbiota transplantation (FMT), have shown promise restoring microbial balance alleviating symptoms, especially PD. Additionally, nutritional interventions probiotics, prebiotics, specialized diets are being investigated for their ability modify improve patient outcomes. highlights therapeutic potential modulation but emphasizes need further clinical trials establish safety efficacy these mental disorders.

Language: Английский

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Smoking, coffee intake, and Parkinson’s disease: potential protective mechanisms and components

NeuroToxicology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Parkinson's disease (PD) is a common progressive neurodegenerative characterized by the loss of dopaminergic neurons in substantia nigra pars compacta (SNpc). Environmental and lifestyle factors, such as smoking coffee drinking, have been associated with decreased risk for PD. However, biological mechanisms underlying protective effects on PD are still not fully understood. It has suggested that non-nicotine components cigarette smoke non-caffeine may contribute to this effect. The aim review was explore candidate molecules behind drinking integrating findings from previous studies. By cross-referencing an index tobacco constituents list existing literature natural compounds their structural analogs show inhibitory activities against monoamine oxidase B, catechol O-methyltransferase, α-synuclein fibrillation, we identified inhibit these targets. Furthermore, potentially play roles suppressing neuroinflammation, activating Nrf2 pathway activators, altering gut microbiome. This suggests phenolic investigated low incidence smokers drinkers, showing moderate strong potential therapeutic interventions. current multifunctional found neuroprotective effects, but none data indicates multifunctionality required effects. will deepen our understanding how linked reduced also be important elucidating

Language: Английский

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