Inflammation and immune dysfunction in Parkinson disease

Nature reviews. Immunology, Год журнала: 2022, Номер 22(11), С. 657 - 673

Опубликована: Март 4, 2022

Язык: Английский

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Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Сен. 22, 2023

Abstract Microglia activation is observed in various neurodegenerative diseases. Recent advances single-cell technologies have revealed that these reactive microglia were with high spatial and temporal heterogeneity. Some identified specific states correlate pathological hallmarks are associated functions. both exert protective function by phagocytosing clearing protein aggregates play detrimental roles due to excessive uptake of aggregates, which would lead microglial phagocytic ability impairment, neuroinflammation, eventually neurodegeneration. In addition, peripheral immune cells infiltration shapes into a pro-inflammatory phenotype accelerates disease progression. also act as mobile vehicle propagate aggregates. Extracellular vesicles released from autophagy impairment all contribute progression Thus, enhancing phagocytosis, reducing microglial-mediated inhibiting exosome synthesis secretion, promoting conversion considered be promising strategies for the therapy Here we comprehensively review biology diseases, including Alzheimer’s disease, Parkinson’s multiple system atrophy, amyotrophic lateral sclerosis, frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration, dementia Lewy bodies Huntington’s disease. We summarize possible microglia-targeted interventions treatments against diseases preclinical clinical evidence cell experiments, animal studies, trials.

Язык: Английский

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Microglia Mediated Neuroinflammation in Parkinson’s Disease

Cells, Год журнала: 2023, Номер 12(7), С. 1012 - 1012

Опубликована: Март 25, 2023

Parkinson’s Disease (PD) is the second most common neurodegenerative disorder seen, especially in elderly. Tremor, shaking, movement problems, and difficulty with balance coordination are among hallmarks, dopaminergic neuronal loss substantia nigra pars compacta of brain aggregation intracellular protein α-synuclein pathological characterizations. Neuroinflammation has emerged as an involving mechanism at initiation development PD. It a complex network interactions comprising immune non-immune cells addition to mediators response. Microglia, resident macrophages CNS, take on leading role regulating neuroinflammation maintaining homeostasis. Under normal physiological conditions, they exist “homeostatic” but upon stimuli, switch “reactive state”. Pro-inflammatory (M1) anti-inflammatory (M2) phenotypes used classify microglial activity each phenotype having its own markers released mediators. When M1 microglia persistent, will contribute various inflammatory diseases, including such In this review, we focus mediated PD also signaling pathways, receptors, involved process, presenting studies that associate microglia-mediated inflammation A better understanding important seeking new therapies for possibly other diseases.

Язык: Английский

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Gut liver brain axis in diseases: the implications for therapeutic interventions

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Дек. 6, 2023

Gut-liver-brain axis is a three-way highway of information interaction system among the gastrointestinal tract, liver, and nervous systems. In past few decades, breakthrough progress has been made in gut liver brain axis, mainly through understanding its formation mechanism increasing treatment strategies. this review, we discuss various complex networks including barrier permeability, hormones, microbial metabolites, vagus nerve, neurotransmitters, immunity, toxic β-amyloid (Aβ) metabolism, epigenetic regulation gut-liver-brain axis. Some therapies containing antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), polyphenols, low FODMAP diet nanotechnology application regulate Besides, some special treatments targeting gut-liver include farnesoid X receptor (FXR) agonists, takeda G protein-coupled 5 (TGR5) glucagon-like peptide-1 (GLP-1) antagonists fibroblast growth factor 19 (FGF19) analogs. Targeting gut-brain embraces cognitive behavioral therapy (CBT), antidepressants tryptophan metabolism-related therapies. liver-brain contains Aβ future, better interactions will promote development novel preventative strategies discovery precise therapeutic targets multiple diseases.

Язык: Английский

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Neuroinflammation and Parkinson’s Disease—From Neurodegeneration to Therapeutic Opportunities

Cells, Год журнала: 2022, Номер 11(18), С. 2908 - 2908

Опубликована: Сен. 17, 2022

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide. Clinically, it characterized by a progressive degeneration of dopaminergic neurons (DAn), resulting in severe motor complications. Preclinical and clinical studies have indicated that neuroinflammation can play role PD pathophysiology, being associated with its onset progression. Nevertheless, several key points concerning neuroinflammatory process remain to be answered. Bearing this mind, present review, we cover impact on exploring inflammatory cells (i.e., microglia astrocytes) interconnections between brain peripheral system. Furthermore, discuss both innate adaptive immune responses regarding pathology explore gut-brain axis communication influence progression disease.

Язык: Английский

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Associations of complete blood cell count-derived inflammatory biomarkers with asthma and mortality in adults: a population-based study

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Июль 28, 2023

This study aims to assess the associations of complete blood cell count (CBC)-derived inflammatory biomarkers with prevalence asthma and mortality.Data was collected from 1999-2018 National Health Nutrition Examination Survey (NHANES). Mortality identified using Death Index until December 31, 2019. The analyzed relationship between CBC-derived biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte (PLR), monocyte-to-lymphocyte (MLR), systemic response index (SIRI), immune-inflammation (SII), multiple logistic regressions. To significance in predicting all-cause respiratory disease mortality patients, Cox proportional regressions random survival forest (RSF) analysis were utilized.A total 48,305 participants included, a mean age 47.27 ± 0.18 years 49.44% male. Among them, 6,403 had asthma, 13.28%. deaths at median follow-up 8.2 (4.5, 12.8) 929 137 respectively. After adjusting for confounders, found be positively associated NLR, PLR, MLR, SIRI SII. Compared lowest quartile, highest quartile NLR (HR=1.765 [1.378-2.262]), MLR (HR=1.717 [1.316-2.241]), (HR=1.796 [1.353-2.383]) SII (HR=1.432 [1.141-1.797]) an increased risk mortality. These more pronounced patients. RSF showed that predictive value adults asthma. sensitivity demonstrated stability our results.The findings suggest are higher

Язык: Английский

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Plasma proteomics identify biomarkers predicting Parkinson’s disease up to 7 years before symptom onset

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

Опубликована: Июнь 18, 2024

Abstract Parkinson’s disease is increasingly prevalent. It progresses from the pre-motor stage (characterised by non-motor symptoms like REM sleep behaviour disorder), to disabling motor stage. We need objective biomarkers for early/pre-motor stages be able intervene and slow underlying neurodegenerative process. Here, we validate a targeted multiplexed mass spectrometry assay blood samples recently diagnosed patients ( n = 99), individuals with isolated disorder (two cohorts: 18 54 longitudinally), healthy controls 36). Our machine-learning model accurately identifies all Parkinson classifies 79% of up 7 years before onset analysing expression eight proteins—Granulin precursor, Mannan-binding-lectin-serine-peptidase-2, Endoplasmatic-reticulum-chaperone-BiP, Prostaglaindin-H2-D-isomaerase, Interceullular-adhesion-molecule-1, Complement C3, Dickkopf-WNT-signalling pathway-inhibitor-3, Plasma-protease-C1-inhibitor. Many these correlate symptom severity. This specific panel indicates molecular events in early could help identify at-risk participants clinical trials aimed at slowing/preventing disease.

Язык: Английский

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The contribution of β-amyloid, Tau and α-synuclein to blood–brain barrier damage in neurodegenerative disorders

Acta Neuropathologica, Год журнала: 2024, Номер 147(1)

Опубликована: Фев. 12, 2024

Abstract Central nervous system (CNS) accumulation of fibrillary deposits made Amyloid β (A ), hyperphosphorylated Tau or α -synuclein ( -syn), present either alone in the form mixed pathology, characterizes most common neurodegenerative diseases (NDDs) as well aging brain. Compelling evidence supports that acute neurological disorders, such traumatic brain injury (TBI) and stroke, are also accompanied by increased deposition toxic A , -syn species. While contribution these pathological proteins to neurodegeneration has been experimentally ascertained, cellular molecular mechanisms driving -syn-related damage remain be fully clarified. In last few years, studies have shown may contribute inducing and/or promoting blood–brain barrier (BBB) disruption. These can affect BBB integrity directly affecting key components pericytes endothelial cells (ECs) indirectly, macrophages activation dysfunction. Here, we summarize critically discuss findings showing how NDDs, TBI stroke. We highlight need for a deeper characterization role dysfunction macrophages, ECs improve diagnosis treatment chronic disorders.

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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The immune system in Parkinson’s disease: what we know so far

Brain, Год журнала: 2024, Номер unknown

Опубликована: Июнь 3, 2024

Abstract Parkinson's disease (PD) is characterised neuropathologically by the degeneration of dopaminergic neurons in ventral midbrain, accumulation α-synuclein (α-syn) aggregates neurons, and chronic neuroinflammation. In past two decades, vitro, ex vivo studies have consistently shown involvement inflammatory responses mediated microglia astrocytes, which may be elicited pathological α-syn or signals from affected other cell types, are directly linked to neurodegeneration development. Besides prominent immune alterations seen central nervous system (CNS), including infiltration T-cells into brain, more recent demonstrated important changes peripheral profile within both innate adaptive compartments, particularly involving monocytes, CD4+ CD8+ T-cells. This review aims integrate consolidated understanding immune-related processes underlying pathogenesis PD, focusing on cells, neuron-glia crosstalk as well central-peripheral interaction during development PD. Our analysis seeks provide a comprehensive view emerging knowledge mechanisms immunity PD implications this for better overall disease.

Язык: Английский

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