Oral and intestinal dysbiosis in Parkinson's disease

Revue Neurologique, Journal Year: 2023, Volume and Issue: 179(9), P. 937 - 946

Published: March 16, 2023

The suspicion of an origin Parkinson's disease (PD) at the periphery body and involvement environmental risk factors in pathogenesis PD have directed attention scientific community towards microbiota. microbiota represents all microorganisms residing both on a host. It plays essential role physiological functioning In this article, we review dysbiosis repeatedly demonstrated how it influences symptoms. Dysbiosis is associated with motor non-motor animal models, only promotes symptoms individuals genetically susceptible to disease, suggesting that factor but not cause disease. We also contributes pathophysiology PD. induces numerous complex metabolic changes, resulting increased intestinal permeability, local systemic inflammation, production bacterial amyloid proteins promote α-synuclein aggregation, as well decrease short-chain fatty acid-producing bacteria anti-inflammatory neuroprotective potential. addition, decreases efficacy dopaminergic treatments. then discuss interest analysis biomarker Finally, give overview interventions modulating gut such dietary interventions, pro-biotics, decontamination fecal transplantation could influence course

Language: Английский

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ASC specks exacerbate α‑synuclein pathology via amplifying NLRP3 inflammasome activities

Journal of Neuroinflammation, Journal Year: 2023, Volume and Issue: 20(1)

Published: Feb. 5, 2023

Inflammasome activation has a pathogenic role in Parkinson's disease (PD). Up-regulated expressions of inflammasome adaptor apoptosis-associated speck-like protein containing CARD (ASC) and assembly ASC specks have been observed postmortems human PD brains experimental models. Extracellular behave like danger signals sustain prolonged activation. However, the contribution propagation pathological progression not fully established.Herein, we used A53T mutant α-synuclein preformed fibrils (PFFs)-stimulated microglia vitro unilateral striatal stereotaxic injection PFFs-induced mice model vivo, to investigate significance progression. Rotarod open-field tests were performed measure motor behaviors indicated mice. Changes molecular expression evaluated by immunofluorescence immunoblotting (IB). Intracellular knockdown BV2 cells was using si-RNA. Microglial neuronal co-cultured trans-well system determine effects on cytoprotection.We direct relationship between levels misfolded α‑synuclein aggregates brains. amplified NLRP3 driven PFFs stimulation, which aggravated reactive microgliosis accelerated pathology, dopaminergic neurodegeneration deficits. Endogenous suppressed microglial aggregation.In conclusion, our study elucidated that contribute activation-associated pathology PD, forms basis for targeting as potential therapy PD.

Language: Английский

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Systemic inflammation and risk of Parkinson’s disease: A prospective cohort study and genetic analysis

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 117, P. 447 - 455

Published: Feb. 7, 2024

Language: Английский

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Sex-specific biphasic alpha-synuclein response and alterations of interneurons in a COVID-19 hamster model

EBioMedicine, Journal Year: 2024, Volume and Issue: 105, P. 105191 - 105191

Published: June 13, 2024

Coronavirus disease 2019 (COVID-19) frequently leads to neurological complications after recovery from acute infection, with higher prevalence in women. However, mechanisms by which SARS-CoV-2 disrupts brain function remain unclear and treatment strategies are lacking. We previously demonstrated neuroinflammation the olfactory bulb of intranasally infected hamsters, followed alpha-synuclein tau accumulation cortex, thus mirroring pathogenesis neurodegenerative diseases such as Parkinson's or Alzheimer's disease.

Language: Английский

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Ultrastructural localization of Porphyromonas gingivalis gingipains in the substantia nigra of Parkinson’s disease brains

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

Published: April 25, 2024

Gingipains are protease virulence factors produced by Porphyromonas gingivalis, a Gram-negative bacterium best known for its role in chronic periodontitis. were recently identified the middle temporal gyrus of postmortem Alzheimer's disease (AD) brains, where gingipain load correlated with AD diagnosis and tau ubiquitin pathology. Since Parkinson's (PD) share some overlapping pathologic features, including nigral pathology Lewy bodies, current study explored whether gingipains present substantia nigra pars compacta PD brains. In immunohistochemical techniques multi-channel fluorescence studies, antigens abundant dopaminergic neurons both neurologically normal control 3-dimensional reconstructions body containing revealed that associated periphery alpha-synuclein aggregates but occasionally observed inside aggregates. vitro proteomic analysis demonstrated recombinant is cleaved lysine-gingipain, generating multiple fragments non-amyloid component fragments. Immunogold electron microscopy co-labeling confirmed occasional colocalization phosphorylated (pSER129) alpha-synuclein. neurons, localized to perinuclear cytoplasm, neuromelanin, mitochondria, nucleus. These data suggest localize interact

Language: Английский

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Dopamine Transmission Imbalance in Neuroinflammation: Perspectives on Long-Term COVID-19

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5618 - 5618

Published: March 15, 2023

Dopamine (DA) is a key neurotransmitter in the basal ganglia, implicated control of movement and motivation. Alteration DA levels central Parkinson’s disease (PD), common neurodegenerative disorder characterized by motor non-motor manifestations deposition alpha-synuclein (α-syn) aggregates. Previous studies have hypothesized link between PD viral infections. Indeed, different cases parkinsonism been reported following COVID-19. However, whether SARS-CoV-2 may trigger process still matter debate. Interestingly, evidence brain inflammation has described postmortem samples patients infected SARS-CoV-2, which suggests immune-mediated mechanisms triggering neurological sequelae. In this review, we discuss role proinflammatory molecules such as cytokines, chemokines, oxygen reactive species modulating homeostasis. Moreover, review existing literature on possible mechanistic interplay SARS-CoV-2-mediated neuroinflammation nigrostriatal DAergic impairment, cross-talk with aberrant α-syn metabolism.

Language: Английский

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alpha-synuclein, autophagy-lysosomal pathway, and Lewy bodies: mutations, propagation, aggregation, and the formation of inclusions

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: 300(10), P. 107742 - 107742

Published: Sept. 2, 2024

Research into the pathophysiology of Parkinson's disease (PD) is a fast-paced pursuit, with new findings about PD and other synucleinopathies being made each year. The involvement various lysosomal proteins, such as TFEB, TMEM175, GBA, LAMP1/2, marks rising awareness importance lysosomes in neurodegenerative disorders. This, along recent developments regarding microglia immune system diseases, has brought era neurodegeneration: role proinflammatory cytokines on nervous system, their downstream effects mitochondria, degradation, autophagy. More effort needed to understand interplay between neuroimmunology mechanisms, many mechanisms remain enigmatic. α-synuclein, key protein main component Lewy bodies, sits at nexus autophagy, cellular stress, neuroimmunology, pathophysiology, progression. This review revisits some fundamental knowledge while capturing latest trends research, specifically it relates α-synuclein.

Language: Английский

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Mucosal Immunity and the Gut-Microbiota-Brain-Axis in Neuroimmune Disease

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(21), P. 13328 - 13328

Published: Nov. 1, 2022

Recent advances in next-generation sequencing (NGS) technologies have opened the door to a wellspring of information regarding composition gut microbiota. Leveraging NGS technology, early metagenomic studies revealed that several diseases, such as Alzheimer’s disease, Parkinson’s autism, and myalgic encephalomyelitis, are characterized by alterations diversity gut-associated microbes. More recently, interest has shifted toward understanding how these microbes impact their host, with special emphasis on interactions brain. Such typically occur either systemically, through production small molecules released into circulation, or signaling via vagus nerves which directly connect enteric nervous system central system. Collectively, this communication is now commonly referred gut-microbiota-brain axis. While equally important, little attention focused causes Although factors can contribute, mucosal immunity plays significant role shaping microbiota both healthy individuals association diseases. The purpose review provide brief overview components then discuss altered immunological conditions may shape consequently affect neuroimmune using select group common diseases examples.

Language: Английский

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The Role of ΔFosB in the Pathogenesis of Levodopa-Induced Dyskinesia: Mechanisms and Therapeutic Strategies

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

Language: Английский

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Rotenone Induces Parkinsonism with Constipation Symptoms in Mice by Disrupting the Gut Microecosystem, Inhibiting the PI3K-AKT Signaling Pathway and Gastrointestinal Motility

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2079 - 2079

Published: Feb. 27, 2025

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Constipation a prodromal symptom PD. It important to investigate pathogenesis constipation symptoms in Rotenone has been successfully used establish PD animal models. However, specific mechanism rotenone-induced not well understood. In this work, we found that appeared earlier than motor impairment mice gavaged with low dose rotenone (30 mg/kg·BW). only caused loss dopaminergic neurons and accumulation α-synuclein, but also significantly reduced serum 5-HT levels 5-HTR4 striatum colon. The mRNA expression aquaporins, gastrointestinal motility factors (c-Kit, Cx43, smMLCK MLC-3) mouse colon was regulated by rotenone. addition, both brain showed inflammation barrier dysfunction; PI3K/AKT pathway substantia nigra inhibited Importantly, structure, composition function gut microbiota were altered Some taxa closely associated symptoms, inflammation, status mice. Akkermansia, Staphylococcus Lachnospiraceae_UCG-006 may play role exacerbating whereas Acinetobacter, Lactobacillus, Bifidobacterium, Solibacillus Eubacterium_xylanophilum_groups be beneficial stimulating peristalsis, maintaining alleviating damage conclusion, low-dose can cause parkinsonism disrupting intestinal microecosystem inhibiting PI3K-AKT motility.

Language: Английский

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