Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Фев. 16, 2024

Abstract The human gastrointestinal tract is populated with a diverse microbial community. vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect biology, including health maintenance, development, aging, disease. advent new sequencing technologies culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations shed light on microbiome–host interactions. Evidence unveiled bidirectional communication between central nervous system, referred as “microbiota–gut–brain axis”. microbiota–gut–brain axis represents an important regulator glial functions, making it actionable target ameliorate development progression neurodegenerative diseases. In this review, we discuss mechanisms As provides essential cues microglia, astrocytes, oligodendrocytes, examine communications microbiota these cells during healthy states Subsequently, diseases using metabolite-centric approach, while also examining role microbiota-related neurotransmitters hormones. Next, targeting intestinal barrier, blood–brain meninges, peripheral immune system counteract dysfunction neurodegeneration. Finally, conclude by assessing pre-clinical clinical evidence probiotics, prebiotics, fecal transplantation A thorough comprehension will foster effective therapeutic interventions for management

Язык: Английский

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Innate immune activation in neurodegenerative diseases

Immunity, Год журнала: 2024, Номер 57(4), С. 790 - 814

Опубликована: Апрель 1, 2024

Язык: Английский

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Microglial activation states and their implications for Alzheimer's Disease

The Journal of Prevention of Alzheimer s Disease, Год журнала: 2025, Номер 12(1), С. 100013 - 100013

Опубликована: Янв. 1, 2025

Alzheimer's Disease (AD) is a chronic neurodegenerative disorder characterized by the accumulation of toxic amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs) tau protein in brain. Microglia, key immune cells central nervous system, play an important role AD development progression, primarily through their responses to Aβ NFTs. Initially, microglia can clear Aβ, but AD, activation overwhelms protective mechanisms, leading sustained neuroinflammation that enhances plaque toxicity, setting off damaging cycle affects neurons, astrocytes, cerebral vasculature, other microglia. Current treatments have been largely ineffective, though emerging immunotherapies focusing on removal show promise, often overlook neuroinflammation. Activated display complex range phenotypes be broadly broken into pro- or anti-inflammatory states, although this dichotomy does not describe significant overlap between states. strongly induce inflammatory activity, triggering production reactive oxygen species, cytokines (e.g., TNF-α, IL-1β, IL-6), synapse engulfment, blood-brain barrier compromise, impaired clearance. These processes contribute neural tissue loss, manifesting as cognitive decline such executive function memory. Conversely, exerts neuroprotective effects suppressing pathways releasing neurotrophic factors aid neuron repair protection. Induction states may offer dual therapeutic approach address both AD. This suggests potential strategies modulate microglial phenotypes, aiming restore functions mitigate disease progression simultaneously targeting inflammation pathology.

Язык: Английский

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Maximizing the benefit and managing the risk of anti-amyloid monoclonal antibody therapy for Alzheimer's disease: Strategies and research directions

Neurotherapeutics, Год журнала: 2025, Номер unknown, С. e00570 - e00570

Опубликована: Март 1, 2025

Язык: Английский

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Periodontal Pathogens and Their Links to Neuroinflammation and Neurodegeneration

Microorganisms, Год журнала: 2023, Номер 11(7), С. 1832 - 1832

Опубликована: Июль 18, 2023

Pathogens that play a role in the development and progression of periodontitis have gained significant attention due to their implications onset various systemic diseases. Periodontitis is characterized as an inflammatory disease gingival tissue mainly caused by bacterial pathogens. Among them, Porphyromonas gingivalis, Treponema denticola, Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans, Tannerella forsythia are regarded main periodontal These pathogens elicit release cytokines, which combination with virulence factors induce chronic inflammation subsequently impact neural function while also altering permeability blood–brain barrier. The primary objective this review summarize existing information regarding pathogens, factors, potential association neuroinflammation neurodegenerative We systematically reviewed longitudinal studies investigated between disorders. Out 24 examined, 20 showed some degree positive correlation disorders, focusing on cognitive demonstrating most robust effects. Therefore, might represent exciting new approach develop novel preventive treatments for

Язык: Английский

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Blood–Brain Barrier Breakdown in Neuroinflammation: Current In Vitro Models

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(16), С. 12699 - 12699

Опубликована: Авг. 11, 2023

The blood-brain barrier, which is formed by tightly interconnected microvascular endothelial cells, separates the brain from peripheral circulation. Together with other central nervous system-resident cell types, including pericytes and astrocytes, barrier forms neurovascular unit. Upon neuroinflammation, this becomes leaky, allowing molecules cells to enter potentially harm tissue of system. Despite significance animal models in research, they may not always adequately reflect human pathophysiology. Therefore, are needed. This review will provide an overview terms both health disease. It describe all key elements vitro explore how different compositions can be utilized effectively model a variety neuroinflammatory conditions. Furthermore, it existing types that used basic research study respective pathologies thus far.

Язык: Английский

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Extracellular vesicles set the stage for brain plasticity and recovery by multimodal signalling

Brain, Год журнала: 2023, Номер unknown

Опубликована: Сен. 28, 2023

Abstract Extracellular vesicles (EVs) are extremely versatile naturally occurring membrane particles that convey complex signals between cells. EVs of different cellular sources capable inducing striking therapeutic responses in neurological disease models. Differently from pharmacological compounds act by modulating defined signalling pathways, EV-based therapeutics possess multiple abilities via a variety effectors, thus allowing the modulation processes may have very potent effects on brain tissue recovery. When applied vivo experimental models diseases, revealed remarkable immune responses, cell metabolism and neuronal plasticity. This multimodal neuroimmune networks profoundly influences highly synergistic context-dependent way. Ultimately, EV-mediated restoration functions helps to set stage for With this review we first outline current understanding mechanisms action EVs, describing how released various identify their targets recipient Then, applicable key conditions such as stroke, sclerosis neurodegenerative diseases presented. Pathways deserve attention specific contexts discussed. We subsequently showcase considerations about EV biodistribution delineate genetic engineering strategies aiming at enhancing uptake signalling. By sketching broad view EV-orchestrated plasticity recovery, finally define possible future clinical applications propose necessary information be provided ahead trials. Our goal is provide steppingstone can used critically discuss next generation diseases.

Язык: Английский

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Overlapping Neuroimmune Mechanisms and Therapeutic Targets in Neurodegenerative Disorders

Biomedicines, Год журнала: 2023, Номер 11(10), С. 2793 - 2793

Опубликована: Окт. 14, 2023

Many potential immune therapeutic targets are similarly affected in adult-onset neurodegenerative diseases, such as Alzheimer's (AD) disease, Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD), well a seemingly distinct Niemann-Pick type C with primarily juvenile onset. This strongly argues for an overlap pathogenic mechanisms. The commonly researched include various cell subsets, microglia, peripheral macrophages, regulatory T cells (Tregs); the complement system; other soluble factors. In this review, we compare these diseases from clinical point of view highlight common pathways mechanisms protein aggregation, neurodegeneration, and/or neuroinflammation that could potentially lead to shared treatment strategies overlapping dysfunctions diseases. These approaches but not limited immunisation, cascade blockade, microbiome regulation, inhibition signal transduction, Treg boosting, stem transplantation.

Язык: Английский

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Immunological Profile and Markers of Endothelial Dysfunction in Elderly Patients with Cognitive Impairments

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(3), С. 1888 - 1888

Опубликована: Фев. 4, 2024

The process of aging is accompanied by a dynamic restructuring the immune response, phenomenon known as immunosenescence. Further, damage to endothelium can be both cause and consequence many diseases, especially in elderly people. purpose this study was carry out immunological biochemical profiling people with acute ischemic stroke (AIS), chronic cerebral circulation insufficiency (CCCI), prediabetes or newly diagnosed type II diabetes mellitus (DM), subcortical vascular dementia (SIVD). Socio-demographic, lifestyle, cognitive data were obtained. Biochemical, hematological, analyses carried out, extracellular vesicles (EVs) endothelial CD markers assessed. greatest number significant deviations from conditionally healthy donors (HDs) same age registered SIVD group, total 20, which 12 specific six non-specific but maximal differences (as compared other three groups) HDs group. for MOCA (Montreal Cognitive Impairment Scale), MMSE (Mini Mental State Examination) life satisfaction self-assessment scores, decrease albumin levels, ADAMTS13 (a Disintegrin Metalloproteinase Thrombospondin Type 1 motif, member 13) activity, an increase VWF (von Willebrand factor) level. Considering changes parameters (mostly Th17-like cells) (CD144 CD34), repair impaired extent DM AIS patients showed HD controls, including These high NEFAs (non-esterified fatty acids) CD31 CD147 EVs. lowest CCCI nine total. There controls no specifics just one difference control parameters, α1-AGP (alpha acid glycoprotein, orosomucoid). Besides patients, impairments also complete absence such (SIVD group). On hand, microvascular seemed latter considering indicators ADAMTS13. In maximum response registered, mainly cells. reaction not pronounced groups may indicate initial stages and/or compensatory nature organic (remodeling). At time, indicated persistent remodeling microvessels, inflammation, anabolic function liver tissues. obtained support two interrelated assumptions. Taking into account primary factors that trigger pathological processes associated pathology related first assumption purine degradation skeletal muscle major factor production uric acid, followed its non-muscle cells, main are Another therapeutic levels progenitor cells have effect reducing risk cerebrovascular disease neurodegenerative diseases.

Язык: Английский

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Microglia depletion reduces neurodegeneration and remodels extracellular matrix in a mouse Parkinson’s disease model triggered by α-synuclein overexpression

npj Parkinson s Disease, Год журнала: 2025, Номер 11(1)

Опубликована: Янв. 9, 2025

Chronic neuroinflammation with sustained microglial activation occurs in Parkinson's disease (PD), yet the mechanisms and exact contribution of these cells to neurodegeneration remains poorly understood. In this study, we induced progressive dopaminergic neuron loss mice via rAAV-hSYN injection cause neuronal expression α-synuclein, which produced behavioral alterations. We administered PLX5622, a colony-stimulating factor 1 receptor inhibitor, for 3 weeks prior injection, maintaining it 8 eliminate microglia. This chronic treatment paradigm prevented development motor deficits concomitantly preserved cell weakened α-synuclein phosphorylation. Gene profiles related extracellular matrix (ECM) remodeling were increased after microglia depletion PD mice, further validated on protein level. demonstrated that exert adverse effects during α-synuclein-overexpression-induced lesion formation, their remodels ECM aids recovery following insult.

Язык: Английский

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