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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Blood-Brain Barrier: From Physiology to Disease and Back

Physiological Reviews, Journal Year: 2018, Volume and Issue: 99(1), P. 21 - 78

Published: Oct. 3, 2018

The blood-brain barrier (BBB) prevents neurotoxic plasma components, blood cells, and pathogens from entering the brain. At same time, BBB regulates transport of molecules into out central nervous system (CNS), which maintains tightly controlled chemical composition neuronal milieu that is required for proper functioning. In this review, we first examine molecular cellular mechanisms underlying establishment BBB. Then, focus on physiology, endothelial pericyte transporters, perivascular paravascular transport. Next, discuss rare human monogenic neurological disorders with primary genetic defect in BBB-associated cells demonstrating link between breakdown neurodegeneration. review effects genes inheritance and/or increased susceptibility Alzheimer's disease (AD), Parkinson's (PD), Huntington's disease, amyotrophic lateral sclerosis (ALS) relation to other pathologies deficits. We next how dysfunction relates deficits majority sporadic AD, PD, ALS cases, multiple sclerosis, neurodegenerative disorders, acute CNS such as stroke, traumatic brain injury, spinal cord epilepsy. Lastly, BBB-based therapeutic opportunities. conclude lessons learned future directions, emphasis technological advances investigate functions living brain, at level, address key unanswered questions.

Language: Английский

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Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes

Translational Neurodegeneration, Journal Year: 2020, Volume and Issue: 9(1)

Published: Nov. 26, 2020

Abstract Neuroinflammation is associated with neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s and amyotrophic lateral sclerosis. Microglia astrocytes are key regulators of inflammatory responses in the central nervous system. The activation microglia heterogeneous traditionally categorized neurotoxic (M1-phenotype A1-phenotype astrocytes) or neuroprotective (M2-phenotype A2-phenotype astrocytes). However, this dichotomized classification may not reflect various phenotypes astrocytes. relationship between these activated glial cells also very complicated, phenotypic distribution can change, based on progression diseases. A better understanding roles diseases essential for developing effective therapies. In review, we discuss response focusing contributions their relationship. addition, biomarkers to measure neuroinflammation studies therapeutic drugs that modulate neuroinflammation.

Language: Английский

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Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson’s disease

Nature Medicine, Journal Year: 2018, Volume and Issue: 24(7), P. 931 - 938

Published: June 8, 2018

Language: Английский

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Microglial control of astrocytes in response to microbial metabolites

Nature, Journal Year: 2018, Volume and Issue: 557(7707), P. 724 - 728

Published: May 1, 2018

Language: Английский

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Inflammation in CNS neurodegenerative diseases

Immunology, Journal Year: 2018, Volume and Issue: 154(2), P. 204 - 219

Published: March 7, 2018

Neurodegenerative diseases, the leading cause of morbidity and disability, are gaining increased attention as they impose a considerable socioeconomic impact, due in part to ageing community. Neuronal damage is pathological hallmark Alzheimer's Parkinson's amyotrophic lateral sclerosis, Huntington's disease, spinocerebellar ataxia multiple although such also observed following neurotropic viral infections, stroke, genetic white matter diseases paraneoplastic disorders. Despite different aetiologies, for example, mutations, trauma protein aggregations, neuronal frequently associated with chronic activation an innate immune response CNS. The growing awareness that system inextricably involved shaping brain during development well mediating damage, but regeneration repair, has stimulated therapeutic approaches modulate neurodegenerative diseases. Here, we review current understanding how astrocytes microglia, neurons oligodendrocytes, shape neuroimmune development, aberrant responses arise or environmental triggers may predispose CNS We discuss known interactions between peripheral brain, concepts on cells enter leave A better disease will be key further manipulating these effective therapies improve quality life, reduce impact neuroinflammatory degenerative

Language: Английский

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Neuroinflammation and depression: A review

European Journal of Neuroscience, Journal Year: 2020, Volume and Issue: 53(1), P. 151 - 171

Published: March 9, 2020

Abstract Some recent clinical and preclinical evidence suggests that neuroinflammation is a key factor interacts with the three neurobiological correlates of major depressive disorder: depletion brain serotonin, dysregulation hypothalamus–pituitary–adrenal (HPA) axis alteration continuous production adult‐generated neurons in dentate gyrus hippocampus. This review discusses main players immunity as well how inflammation above mechanisms. It reported kynurenine (KYN) pathway favour its excitotoxic component HPA have common effect increasing extracellular glutamate levels neurotransmission, which can impact hippocampal neurogenesis. pathophysiological cascade appears to be triggered or sustained reinforced by any chronic inflammatory condition involving increased circulating markers are able cross blood–brain barrier activate microglia; it also consequence primary neuroinflammation, such neurodegenerative disorders early manifestations frequently symptoms. Further data indicate microglial activation may result from direct stress on vascular function. The intricated dynamic crosstalk between other relevant depression add therapeutic target for future strategies disorder.

Language: Английский

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Overview of General and Discriminating Markers of Differential Microglia Phenotypes

Frontiers in Cellular Neuroscience, Journal Year: 2020, Volume and Issue: 14

Published: Aug. 6, 2020

Inflammatory processes and microglia activation accompanies most of the pathophysiological diseases in central nervous system. It is proven that glial pathology precedes even drives development multiple neurodegenerative conditions. A growing number studies point out importance brain as well physiological functioning. Those resident immune cells are divergent from peripherally infiltrated macrophages, but their precise situ discrimination surprisingly difficult. Microglia heterogeneity visible especially morphology, cell density particular structures, also expression cellular markers. This often determines role physiology or The species differences between rodent human markers add complexity to whole picture. Furthermore, due activation, shows a broad spectrum phenotypes ranging pro-inflammatory, potentially cytotoxic M1, anti-inflammatory, scavenging regenerative M2. distinction specific nowadays essential study microglial functions tissue state such quickly changing environment. Due overwhelming data on sets available for studies, choice appropriate scientific challenge. review gathers, classifies describes known recently discovered protein expressed by different phenotypes. Presented include qualitative semi-quantitative, general specific, surface intracellular proteins secreted molecules. Information provided here creates comprehensive practical guide trough current knowledge will allow choose proper, more detailed neuroinflammatory mechanisms various, physiological, pathological, Both, basic research clinical medicine, need clearly described validated molecular phenotype, diagnostics, treatment prevention engaging glia activation.

Language: Английский

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Astrocyte Crosstalk in CNS Inflammation

Neuron, Journal Year: 2020, Volume and Issue: 108(4), P. 608 - 622

Published: Sept. 7, 2020

Language: Английский

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Moving beyond the glial scar for spinal cord repair

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Aug. 28, 2019

Abstract Traumatic spinal cord injury results in severe and irreversible loss of function. The triggers a complex cascade inflammatory pathological processes, culminating formation scar. While traditionally referred to as glial scar, the scar fact comprises multiple cellular extracellular components. This multidimensional nature should be considered when aiming understand role scarring limiting tissue repair recovery. In this Review we discuss recent advances understanding composition phenotypic characteristics oversimplification defining binary terms good or bad, development therapeutic approaches target components enable improved functional outcome after injury.

Language: Английский

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