Microglia in Neurological Diseases: A Road Map to Brain-Disease Dependent-Inflammatory Response

Frontiers in Cellular Neuroscience, Journal Year: 2018, Volume and Issue: 12

Published: Dec. 18, 2018

Microglia represent a specialized population of macrophages-like cells in the central nervous system (CNS) considered immune sentinels that are capable orchestrating potent inflammatory response. also involved synaptic organizatio, trophic neuronal support during development, phagocytosis apoptotic developing brain, myelin turnover, control excitability, phagocytic debris removal as well brain protection and repair. Microglial response is pathology dependent affects to immune, metabolic. In this review, we will shed light on microglial activation depending disease context influence factors such aging, environment or cell-to-cell interaction.

Language: Английский

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Anti-inflammatory effects of flavonoids in neurodegenerative disorders

European Journal of Medicinal Chemistry, Journal Year: 2017, Volume and Issue: 153, P. 105 - 115

Published: Sept. 7, 2017

Language: Английский

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An Inflammation-Centric View of Neurological Disease: Beyond the Neuron

Frontiers in Cellular Neuroscience, Journal Year: 2018, Volume and Issue: 12

Published: March 21, 2018

Inflammation is a complex biological response fundamental to how the body deals with injury and infection eliminate initial cause of cell effect repair. Unlike normally beneficial acute inflammatory response, chronic inflammation can lead tissue damage ultimately its destruction, often results from an inappropriate immune response. in nervous system ('neuroinflammation'), especially when prolonged, be particularly injurious. While per se may not disease, it contributes importantly disease pathogenesis across both peripheral (neuropathic pain, fibromyalgia) central (e.g. Alzheimer Parkinson multiple sclerosis, motor neuron disease. ischemia traumatic brain injury, depression, autism spectrum disorder) systems. The existence extensive lines communication between represents principle underlying neuroinflammation. Immune cell-derived molecules are critical for regulation host responses inflammation. Although these mediators originate various non-neuronal cells, important sources above neuropathologies appear microglia mast together astrocytes possibly also oligodendrocytes. Understanding neuroinflammation requires appreciation that – interactions, glia cells themselves, integral part process. Within this context occupies key niche orchestrating process, initiation prolongation. This review will describe current state knowledge concerning biology neuroinflammation, emphasizing cell-glia glia-glia then conclude consideration cell’s endogenous mechanisms might leveraged provide therapeutic strategy target

Language: Английский

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Brain and Peripheral Atypical Inflammatory Mediators Potentiate Neuroinflammation and Neurodegeneration

Frontiers in Cellular Neuroscience, Journal Year: 2017, Volume and Issue: 11

Published: July 23, 2017

Neuroinflammatory response is primarily a protective mechanism in the brain. However, excessive and chronic inflammatory responses can lead to deleterious effects involving immune cells, brain cells signaling molecules. Neuroinflammation induces accelerates pathogenesis of Parkinson's disease (PD), Alzheimer's (AD) Multiple Sclerosis. pathways are indicated as novel therapeutic targets for these diseases. Mast hematopoietic origin that regulate inflammation upon activation release many proinflammatory mediators systemic central nervous system conditions. In addition, released from activated glial induce neurodegeneration Systemic inflammation-derived cytokines/chemokines other factors cause breach blood brain-barrier (BBB) thereby allowing entry immune/inflammatory including mast cell progenitors, cytokines chemokines into These peripheral-derived intrinsically generated cytokines/chemokines, α-synuclein, corticotropin-releasing hormone, substance P, beta amyloid 1-42 (Aβ1-42) peptide precursor proteins activate T-cells additional neurotoxic molecules contributing neuroinflammation neuronal death. The glia maturation factor, protein discovered our laboratory glia, activates chemokines. Chronic increase Aβ plaque formation AD brains PD brains. Glial reactivate each neuroinflammatory conditions augment neuroinflammation. Further, also enter peripheral through defective BBB, recruit brain, exacerbate We suggest cell-associated could This review addresses role some atypical associated with their neurodegeneration.

Language: Английский

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The integration of inflammaging in age-related diseases

Seminars in Immunology, Journal Year: 2018, Volume and Issue: 40, P. 17 - 35

Published: Oct. 2, 2018

Language: Английский

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Neuroinflammation in Alzheimer’s Disease

Biomedicines, Journal Year: 2021, Volume and Issue: 9(5), P. 524 - 524

Published: May 7, 2021

Alzheimer's disease (AD) is a neurodegenerative associated with human aging. Ten percent of individuals over 65 years have AD and its prevalence continues to rise increasing age. There are currently no effective modifying treatments for AD, resulting in increasingly large socioeconomic personal costs. Increasing age an increase low-grade chronic inflammation (inflammaging) that may contribute the process AD. Although exact mechanisms remain unclear, aberrant elevation reactive oxygen nitrogen species (RONS) levels from several endogenous exogenous processes brain not only affect cell signaling, but also trigger cellular senescence, inflammation, pyroptosis. Moreover, compromised immune privilege allows infiltration peripheral cells infectious agents play role. Additionally, meta-inflammation as well gut microbiota dysbiosis drive neuroinflammatory process. Considering inflammatory/immune pathways dysregulated parallel cognitive dysfunction elucidating relationship between central nervous system facilitate development safe therapy We discuss some current ideas on inflammaging appear summarize details few immunomodulatory strategies being developed selectively target detrimental aspects neuroinflammation without affecting defense against pathogens tissue damage.

Language: Английский

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Microbiota in neuroinflammation and synaptic dysfunction: a focus on Alzheimer’s disease

Molecular Neurodegeneration, Journal Year: 2022, Volume and Issue: 17(1)

Published: March 5, 2022

The implication of gut microbiota in the control brain functions health and disease is a novel, currently emerging concept. Accumulating data suggest that exert its action at least part by modulating neuroinflammation. Given link between neuroinflammatory changes neuronal activity, it plausible may affect indirectly impacting microglia, key player Indeed, increasing evidence suggests interplay microglia synaptic dysfunction involve microbiota, among other factors. In addition to these indirect microglia-dependent actions on has been recently recognized could also activity directly stimulation vagus nerve.

Language: Английский

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Targeting Neuroinflammation to Treat Alzheimer’s Disease

CNS Drugs, Journal Year: 2017, Volume and Issue: 31(12), P. 1057 - 1082

Published: Dec. 1, 2017

Over the past few decades, research on Alzheimer's disease (AD) has focused pathomechanisms linked to two of major pathological hallmarks extracellular deposition beta-amyloid peptides and intra-neuronal formation neurofibrils. Recently, a third component, neuroinflammatory reaction mediated by cerebral innate immune cells, entered spotlight, prompted findings from genetic, pre-clinical, clinical studies. Various proteins that arise during neurodegeneration, including beta-amyloid, tau, heat shock proteins, chromogranin, among others, act as danger-associated molecular patterns, that—upon engagement pattern recognition receptors—induce inflammatory signaling pathways ultimately lead production release mediators. These may have beneficial effects but compromise neuronal function cause cell death. The current review, assembled participants Chiclana Summer School Neuroinflammation 2016, provides an overview our understanding AD-related processes. We describe principal cellular players in inflammation they pertain AD, examine modifying factors, discuss potential future therapeutic targets.

Language: Английский

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Can an Infection Hypothesis Explain the Beta Amyloid Hypothesis of Alzheimer’s Disease?

Frontiers in Aging Neuroscience, Journal Year: 2018, Volume and Issue: 10

Published: July 24, 2018

Alzheimer's disease (AD) is the most frequent type of dementia. The pathological hallmarks are extracellular senile plaques composed beta-amyloid peptide (Aβ) and intracellular neurofibrillary tangles pTau. These findings led to "beta-amyloid hypothesis" that proposes Aβ major cause AD. Clinical trials targeting in brain have mostly failed, whether they attempted decrease production by BACE inhibitors or antibodies. failures suggest a need find new hypotheses explain AD pathogenesis generate targets for intervention prevent treat disease. Many years ago, "infection was proposed, but received little attention. However, recent discovery an antimicrobial (AMP) acting against bacteria, fungi, viruses gives increased credence infection hypothesis etiology We others shown microbial increases synthesis this AMP. Here, we propose as AMP will be beneficial on first challenge become progressively detrimental becomes chronic reactivates from time time. Furthermore, host measures remove excess over due microglial senescence biofilm formation. aggregates with form patients. In review, develop connection between Infection - discuss future possible treatments based paradigm.

Language: Английский

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Human Inflammaging

Gerontology, Journal Year: 2019, Volume and Issue: 65(5), P. 495 - 504

Published: Jan. 1, 2019

Human aging is a very complex process that occurs in an intricate biological and physiological setting. Many changes occur with among the most important are immune reactivity associated cell differentiation stages phenomenon of inflammaging, understood as subclinical inflammatory readiness, manifested by elevated levels proinflammatory factors. It was stated for long time this tandem parallel or eventually sequentially. However, recent evidence points to fact that, both originate from chronic antigen stimulation, they mutually drive each other. In context, inflammaging considered basis age-related diseases (ARD). review concerning human we argue develop during whole life diverted (excessive) normal reaction specific stressors. Thus, may not be cause these diseases; however, it can trigger clinical manifestation ARD. best intervention should aim regulate balance between pro- anti-inflammatory signals more appropriate stimulations avoid/delay appearance diseases.

Language: Английский

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