Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?

Nature Reviews Neurology, Journal Year: 2020, Volume and Issue: 17(3), P. 157 - 172

Published: Dec. 14, 2020

Language: Английский

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How neuroinflammation contributes to neurodegeneration

Science, Journal Year: 2016, Volume and Issue: 353(6301), P. 777 - 783

Published: Aug. 18, 2016

Neurodegenerative diseases such as Alzheimer's disease, Parkinson's amyotrophic lateral sclerosis, and frontotemporal lobar dementia are among the most pressing problems of developed societies with aging populations. Neurons carry out essential functions signal transmission network integration in central nervous system main targets neurodegenerative disease. In this Review, I address how neuron's environment also contributes to neurodegeneration. Maintaining an optimal milieu for neuronal function rests supportive cells termed glia blood-brain barrier. Accumulating evidence suggests that neurodegeneration occurs part because is affected during disease a cascade processes collectively neuroinflammation. These observations indicate therapies targeting glial might provide benefit those afflicted by disorders.

Language: Английский

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Physiology of Astroglia

Physiological Reviews, Journal Year: 2017, Volume and Issue: 98(1), P. 239 - 389

Published: Dec. 24, 2017

Astrocytes are neural cells of ectodermal, neuroepithelial origin that provide for homeostasis and defense the central nervous system (CNS). highly heterogeneous in morphological appearance; they express a multitude receptors, channels, membrane transporters. This complement underlies their remarkable adaptive plasticity defines functional maintenance CNS development aging. tightly integrated into networks act within context tissue; astrocytes control at all levels organization from molecular to whole organ.

Language: Английский

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The aryl hydrocarbon receptor: an environmental sensor integrating immune responses in health and disease

Nature reviews. Immunology, Journal Year: 2019, Volume and Issue: 19(3), P. 184 - 197

Published: Feb. 4, 2019

Language: Английский

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Impact of microbiota on central nervous system and neurological diseases: the gut-brain axis

Journal of Neuroinflammation, Journal Year: 2019, Volume and Issue: 16(1)

Published: March 1, 2019

Development of central nervous system (CNS) is regulated by both intrinsic and peripheral signals. Previous studies have suggested that environmental factors affect neurological activities under physiological pathological conditions. Although there anatomical separation, emerging evidence has indicated the existence bidirectional interaction between gut microbiota, i.e., (diverse microorganisms colonizing human intestine), brain. The cross-talk microbiota brain may crucial impact during basic neurogenerative processes, in neurodegenerative disorders tumors CNS. In this review, we discuss biological interplay gut-brain axis, further explore how communication be dysregulated diseases. Further, highlight new insights modification composition, which emerge as a promising therapeutic approach to treat CNS disorders.

Language: Английский

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Myelin in the Central Nervous System: Structure, Function, and Pathology

Physiological Reviews, Journal Year: 2019, Volume and Issue: 99(3), P. 1381 - 1431

Published: May 8, 2019

Oligodendrocytes generate multiple layers of myelin membrane around axons the central nervous system to enable fast and efficient nerve conduction. Until recently, saltatory conduction was considered only purpose myelin, but it is now clear that has more functions. In fact, myelinating oligodendrocytes are embedded in a vast network interconnected glial neuronal cells, increasing evidence supports an active role within this assembly, for example, by providing metabolic support neurons, regulating ion water homeostasis, adapting activity-dependent signals. The molecular complexity governing these interactions requires in-depth understanding how interact they generate, maintain, remodel their sheaths. This review deals with biology expanded relationship its underlying neighboring disturbances various diseases such as sclerosis, acute disseminated encephalomyelitis, neuromyelitis optica spectrum disorders. Furthermore, we will highlight specific between astrocytes, oligodendrocytes, microglia contribute demyelination hereditary white matter pathologies.

Language: Английский

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Glial Cells: Role of the Immune Response in Ischemic Stroke

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Feb. 26, 2020

Ischemic stroke, which accounts for 75-80% of strokes, is a predominant cause morbidity and mortality worldwide. Recently, post-stroke immune response becomes new breakthrough the treatment strategy ischemic stroke. Glial cells, including microglia, astrocytes, oligodendrocytes, are major components peri-infarction environment in central nervous system have been elucidated to play critical roles regulation. However, increasing evidences suggest that glial cells exert different, even contrary effect Microglia, survey CNS homostasis regulate innate response, rapidly activated following The microglia would release inflammatory cytokines induce neuronal tissue injuries. On contrary, anti-inflammatory neurotrophic factors secreted by alternatively considered be benefit recovery Astrocytes activation reactive gliosis stroke contribute limitaion brain injury stabalize homeostasis. scar developed astrocytes also hinder reconnectivity extension. Oligodendrocytes shown extensively involved demyelination remyelination after Oligodendrocyte precursor able differentiate into reactived supposed lead functional recovery. Here we discuss mechanisms regulation mediated interaction between neurons. present review, from perspective various describes their possible at different stages future intervention targets.

Language: Английский

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Involvement of Astrocytes in Alzheimer’s Disease from a Neuroinflammatory and Oxidative Stress Perspective

Frontiers in Molecular Neuroscience, Journal Year: 2017, Volume and Issue: 10

Published: Dec. 19, 2017

Alzheimer disease (AD) is a frequent and devastating neurodegenerative in humans, but still no curative treatment has been developed. Although many explicative theories have proposed, precise pathophysiological mechanisms are unknown. Due to the importance of astrocytes brain homeostasis they become interesting targets for study AD. Changes astrocyte function observed brains from individuals with AD, as well AD vitro vivo animal models. The presence amyloid beta (Aβ) shown disrupt gliotransmission, neurotransmitter uptake, alter calcium signaling astrocytes. Furthermore, express apolipoprotein E involved production, degradation removal Aβ. As well, changes that precede other pathological characteristics point an early contribution astroglia this disease. Astrocytes participate inflammatory/immune responses central nervous system. Aβ activates different cell receptors intracellular pathways, mainly advanced glycation end products receptor/nuclear factor kappa-light-chain-enhancer activated B cells (NF-κB) pathway, responsible transcription pro-inflammatory cytokines chemokines release these agents may induce cellular damage or even stimulate production Additionally, induces appearance oxidative stress (OS) reactive oxygen species nitrogen astrocytes, affecting among others, levels, NADPH oxidase (NOX), NF-κB signaling, glutamate uptake (increasing risk excitotoxicity) mitochondrial function. Excessive neuroinflammation OS seem be both. Aβ/NF-κB interaction play role inflammatory present In paper, we also discuss therapeutic measures highlighting pathology. Several new approaches involving phenols (curcumin), phytoestrogens (genistein), neuroesteroids natural phytochemicals explored obtaining some promising results regarding cognitive improvements attenuation neuroinflammation. Novel strategies comprising aimed reduce proposed. These include estrogen receptor agonists (pelargonidin), Bambusae concretio Salicea, Monascin, various antioxidatives such resveratrol, tocotrienol, anthocyanins, epicatechin, showing beneficial effects

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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Leukodystrophies: a proposed classification system based on pathological changes and pathogenetic mechanisms

Acta Neuropathologica, Journal Year: 2017, Volume and Issue: 134(3), P. 351 - 382

Published: June 21, 2017

Leukodystrophies are genetically determined disorders characterized by the selective involvement of central nervous system white matter. Onset may be at any age, from prenatal life to senescence. Many leukodystrophies degenerative in nature, but some only impair matter function. The clinical course is mostly progressive, also static or even improving with time. Progressive often fatal, and no curative treatment known. last decade has witnessed a tremendous increase number defined owing diagnostic approach combining magnetic resonance imaging pattern recognition next generation sequencing. Knowledge on physiology pathology dramatically built up. This led that few due mutations myelin- oligodendrocyte-specific genes, many rather caused defects other structural components, including astrocytes, microglia, axons blood vessels. We here propose novel classification takes into account primary component. Categories this myelin defect oligodendrocytes (hypomyelinating demyelinating leukodystrophies, vacuolization); astrocytopathies; leuko-axonopathies; microgliopathies; leuko-vasculopathies. Following classification, we illustrate neuropathology disease mechanisms taken as example for each category. Some fall more than one Given complex molecular cellular interplay underlying pathology, behind becomes crucial addressing possible strategies.

Language: Английский

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