Microglia and Central Nervous System–Associated Macrophages—From Origin to Disease Modulation DOI
Marco Prinz, Takahiro Masuda, Michael A. Wheeler

et al.

Annual Review of Immunology, Journal Year: 2021, Volume and Issue: 39(1), P. 251 - 277

Published: Feb. 9, 2021

The immune system of the central nervous (CNS) consists primarily innate cells. These are highly specialized macrophages found either in parenchyma, called microglia, or at CNS interfaces, such as leptomeningeal, perivascular, and choroid plexus macrophages. While they were thought phagocytes, their function extends well beyond simple removal cell debris during development diseases. Brain-resident cells to be plastic, long-lived, host an outstanding number risk genes for multiple pathologies. As a result, now considered most suitable targets modulating Additionally, recent single-cell technologies enhanced our molecular understanding origins, fates, interactomes, functional statesduring health perturbation. Here, we review current state challenges myeloid biology treatment options related

Language: Английский

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

Fangda Leng,

Paul Edison

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

Published: Dec. 14, 2020

Language: Английский

Citations

2100
The Bidirectional Relationship of Depression and Inflammation: Double Trouble DOI Creative Commons
Eléonore Beurel, Marisa Toups, Charles B. Nemeroff

et al.

Neuron, Journal Year: 2020, Volume and Issue: 107(2), P. 234 - 256

Published: June 17, 2020

Language: Английский

Citations

1434
Microglia Biology: One Century of Evolving Concepts DOI Creative Commons
Marco Prinz, Steffen Jung, Josef Priller

et al.

Cell, Journal Year: 2019, Volume and Issue: 179(2), P. 292 - 311

Published: Oct. 1, 2019

Language: Английский

Citations

1076
Microglia states and nomenclature: A field at its crossroads DOI Creative Commons
Rosa Chiara Paolicelli, Amanda Sierra, Beth Stevens

et al.

Neuron, Journal Year: 2022, Volume and Issue: 110(21), P. 3458 - 3483

Published: Nov. 1, 2022

Language: Английский

Citations

1065
Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer’s disease DOI
Yingyue Zhou, Wilbur M. Song,

Prabhakar S. Andhey

et al.

Nature Medicine, Journal Year: 2020, Volume and Issue: 26(1), P. 131 - 142

Published: Jan. 1, 2020

Language: Английский

Citations

897
Complex heatmap visualization DOI Creative Commons
Zuguang Gu

iMeta, Journal Year: 2022, Volume and Issue: 1(3)

Published: Aug. 1, 2022

Abstract Heatmap is a widely used statistical visualization method on matrix‐like data to reveal similar patterns shared by subsets of rows and columns. In the R programming language, there are many packages that make heatmaps. Among them, ComplexHeatmap package provides richest toolset for constructing highly customizable can easily establish connections between multisource information automatically concatenating adjusting list heatmaps as well complex annotations, which makes it applied in analysis fields, especially bioinformatics, find hidden structures data. this article, we give comprehensive introduction current state , including its modular design, rich functionalities, broad applications.

Language: Английский

Citations

844
Overview of General and Discriminating Markers of Differential Microglia Phenotypes DOI Creative Commons
Agnieszka M. Jurga, Martyna Paleczna, Katarzyna Kuter

et al.

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

Citations

762
ROS Generation in Microglia: Understanding Oxidative Stress and Inflammation in Neurodegenerative Disease DOI Creative Commons
Dominic S. A. Simpson, Peter L. Oliver

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

Citations

718
Microglia Heterogeneity in the Single-Cell Era DOI Creative Commons
Takahiro Masuda, Roman Sankowski, Ori Staszewski

et al.

Cell Reports, Journal Year: 2020, Volume and Issue: 30(5), P. 1271 - 1281

Published: Feb. 1, 2020

Microglia are resident immune cells in the central nervous system (CNS) that capable of carrying out prominent and various functions during development adulthood under both homeostatic disease conditions. Although microglia traditionally thought to be heterogeneous populations, which potentially allows them achieve a wide range responses environmental changes for maintenance CNS homeostasis, lack unbiased high-throughput methods assess heterogeneity has prevented study spatially temporally distributed subsets. The recent emergence novel single-cell techniques, such as cytometry by time-of-flight mass spectrometry (CyTOF) RNA sequencing, enabled scientists overcome limitations reveal surprising context-dependent microglia. In this review, we summarize current knowledge about spatial, temporal, functional diversity development, mice humans.

Language: Английский

Citations

570
The blood–brain barrier in health and disease: Important unanswered questions DOI Creative Commons
Caterina P. Profaci, Roeben N. Munji,

Robert S. Pulido

et al.

The Journal of Experimental Medicine, Journal Year: 2020, Volume and Issue: 217(4)

Published: March 25, 2020

The blood vessels vascularizing the central nervous system exhibit a series of distinct properties that tightly control movement ions, molecules, and cells between parenchyma. This “blood–brain barrier” is initiated during angiogenesis via signals from surrounding neural environment, its integrity remains vital for homeostasis protection throughout life. Blood–brain barrier dysfunction contributes to pathology in range neurological conditions including multiple sclerosis, stroke, epilepsy, has also been implicated neurodegenerative diseases such as Alzheimer’s disease. review will discuss current knowledge key unanswered questions regarding blood–brain health

Language: Английский

Citations

562