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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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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ROS Generation in Microglia: Understanding Oxidative Stress and Inflammation in Neurodegenerative Disease

Antioxidants, Journal Year: 2020, Volume and Issue: 9(8), P. 743 - 743

Published: Aug. 13, 2020

Neurodegenerative disorders, such as Alzheimer’s disease, are a global public health burden with poorly understood aetiology. Neuroinflammation and oxidative stress (OS) undoubtedly hallmarks of neurodegeneration, contributing to disease progression. Protein aggregation neuronal damage result in the activation disease-associated microglia (DAM) via damage-associated molecular patterns (DAMPs). DAM facilitate persistent inflammation reactive oxygen species (ROS) generation. However, mechanisms linking OS have not been well-defined; thus targeting these cells for clinical benefit has possible. In microglia, ROS generated primarily by NADPH oxidase 2 (NOX2) NOX2 is associated DAMP signalling, amyloid plaque deposition, especially cerebrovasculature. Additionally, originating from both NOX mitochondria may act second messengers propagate immune activation; intracellular signalling underlie excessive OS. Targeting key kinases inflammatory response could cease promote tissue repair. Expression antioxidant proteins dehydrogenase 1 (NQO1), promoted transcription factor Nrf2, which functions control limit Lipid droplet accumulating (LDAM) also represent double-edged sword neurodegenerative sequestering peroxidised lipids non-pathological ageing but becoming dysregulated pro-inflammatory disease. We suggest that future studies should focus on targeted manipulation understand driving inflammatory-related activation. Finally, we discuss recent evidence therapeutic target identification be unbiased founded relevant pathophysiological assays discovery translatable anti-inflammatory therapeutics.

Language: Английский

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Tissue-specific macrophages: how they develop and choreograph tissue biology

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 23(9), P. 563 - 579

Published: March 15, 2023

Macrophages are innate immune cells that form a 3D network in all our tissues, where they phagocytose dying and cell debris, complexes, bacteria other waste products. Simultaneously, produce growth factors signalling molecules — such activities not only promote host protection response to invading microorganisms but also crucial for organ development homeostasis. There is mounting evidence of macrophages orchestrating fundamental physiological processes, as blood vessel formation, adipogenesis, metabolism central peripheral neuronal function. In parallel, novel methodologies have led the characterization tissue-specific macrophages, with distinct subpopulations these showing different developmental trajectories, transcriptional programmes life cycles. Here, we summarize growing knowledge macrophage diversity how subsets orchestrate tissue We further interrelate ontogeny their core functions across is, events within niche may control functionality during development, homeostasis ageing. Finally, highlight open questions will need be addressed by future studies better understand subsets. important immunity infections clearing products from maintain health regulating metabolism, many biological processes. Elvira Mass co-workers discuss populations found throughout body, highlighting shared unique aspects functions.

Language: Английский

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Metabolic Reprograming of Microglia in the Regulation of the Innate Inflammatory Response

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

Published: March 20, 2020

Microglia sustain normal brain functions continuously monitoring cerebral parenchyma to detect neuronal activities and alteration of homeostatic processes. The metabolic pathways involved in microglia activity adapt at contribute cell phenotypes. While the mitochondrial oxidative phosphorylation is highly efficient ATP production, glycolysis enables with a faster rate generation intermediates for growth cytokine production. In macrophages, pro‐inflammatory stimuli induce switch from glycolysis, phenomenon similar Warburg effect well characterized tumor cells. Modification allows macrophages properly respond changing environment many evidence suggest that, similarly microglial cells are capable plastic use energy substrates. Neuroinflammation common condition neurodegenerative diseases reprograming has been reported neurodegeneration. Here we review existing data on metabolism connections neuroinflammatory diseases, highlighting how changes module microglia.

Language: Английский

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Immune Pathways in Etiology, Acute Phase, and Chronic Sequelae of Ischemic Stroke

Circulation Research, Journal Year: 2022, Volume and Issue: 130(8), P. 1167 - 1186

Published: April 14, 2022

Inflammation and immune mechanisms are crucially involved in the pathophysiology of development, acute damage cascades, chronic course after ischemic stroke. Atherosclerosis is an inflammatory disease, and, addition to classical risk factors, maladaptive lead increased Accordingly, individuals with signs inflammation or corresponding biomarkers have Anti-inflammatory drugs, such as IL (interleukin)-1β blockers, methotrexate, colchicine, represent attractive treatment strategies prevent vascular events Lately, COVID-19 pandemic shows a clear association between SARS-CoV2 infections cerebrovascular events. Furthermore, both innate adaptive systems influence cerebral cascades Neutrophils, monocytes, microglia, well T B lymphocytes each play complex interdependent roles that synergize remove dead tissue but also can cause bystander injury intact brain cells generate inflammation. Chronic systemic comorbid may unfavorably outcome stroke recurrence for further In addition, triggers specific depression, which turn promote infections. Recent research now increasingly addressing question extent long-term particular, complications poststroke dementia even depression.

Language: Английский

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The Inflamed Brain in Schizophrenia: The Convergence of Genetic and Environmental Risk Factors That Lead to Uncontrolled Neuroinflammation

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

Published: Aug. 27, 2020

Schizophrenia is a disorder with heterogeneous etiology involving complex interplay between genetic and environmental risk factors. The immune system now known to play vital roles in nervous function pathology through regulating neuronal glial development, synaptic plasticity, behavior. In this regard, the positioned as common link seemingly diverse factors for schizophrenia. Synthesizing information about how immune-brain axis affected by multiple these might interact schizophrenia necessary better understand pathogenesis of disease. Such knowledge will aid development more translatable animal models that may lead effective therapeutic interventions. Here, we provide an overview modulate function. We also explore including exposure pollution, gut dysbiosis, maternal activation early-life stress, consequences are linked microglial dysfunction. propose morphological signaling deficits blood-brain barrier, observed some individuals schizophrenia, can act gateway peripheral central inflammation, thus affecting microglia their essential functions. Finally, describe response neuroinflammation impact on brain homeostasis, well pathophysiology.

Language: Английский

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Genetic analysis of the human microglial transcriptome across brain regions, aging and disease pathologies

Nature Genetics, Journal Year: 2022, Volume and Issue: 54(1), P. 4 - 17

Published: Jan. 1, 2022

Language: Английский

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Single-cell and spatial transcriptomics: deciphering brain complexity in health and disease

Nature Reviews Neurology, Journal Year: 2023, Volume and Issue: 19(6), P. 346 - 362

Published: May 17, 2023

Language: Английский

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Human microglia states are conserved across experimental models and regulate neural stem cell responses in chimeric organoids

Cell stem cell, Journal Year: 2021, Volume and Issue: 28(12), P. 2153 - 2166.e6

Published: Sept. 17, 2021

Language: Английский

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